Cigna oncology value-based pathways
Cigna oncology value-based pathways program was created to promote the use of evidence-based, high value, cancer treatment regimens. Pathway regimens are a subset of regimens recommended by the National Comprehensive Cancer Network® (NCCN) that deliver the best clinical outcomes for patients.
Anal Cancer Pathways:
| Localized Disease: Definitive Chemoradiation
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Recurrent/Metastatic: First Line
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Recurrent/Metastatic: Subsequent Therapy
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References
Localized Disease: Definitive Chemoradiation
- Ajani JA et al. Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA 2008;299:1914-21 Fluorouracil, Mitomycin, and Radiotherapy vs Fluorouracil, Cisplatin, and Radiotherapy for Carcinoma of the Anal Canal: A Randomized Controlled Trial | Cancer Biomarkers | JAMA | JAMA Network
- Flam M et al. Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol 1996; 14:2527-39. Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. | Journal of Clinical Oncology (ascopubs.org)
- Goodman K et al. Capecitabine plus mitomycin in patients undergoing definitive chemoradiation for anal squamous cell carcinoma. Int J Radiat Oncol Phys 2014; 90:S32-S33. Capecitabine Plus Mitomycin in Patients Undergoing Definitive Chemoradiation for Anal Squamous Cell Carcinoma - International Journal of Radiation Oncology, Biology, Physics (redjournal.org)
- Thind G et al. Chemoradiation with capecitabine and mitomycin-C for stage I-III anal squamous cell carcinoma. Ratiat Oncol 2014;9: 124 Chemoradiation with capecitabine and mitomycin-C for stage I-III anal squamous cell carcinoma | Radiation Oncology | Full Text (biomedcentral.com)
- Gunderson LL et al. Long-term update of US GI Intergroup RTOG 98-11 Phase III trial for anal carcinoma: survival, relapse, and colostomy failure with concurrent chemoradiation involving fluorouracil/mitomycin versus fluorouracil/cisplatin. J Clin Oncol 2012; 30:4344-51. Long-Term Update of US GI Intergroup RTOG 98-11 Phase III Trial for Anal Carcinoma: Survival, Relapse, and Colostomy Failure With Concurrent Chemoradiation Involving Fluorouracil/Mitomycin Versus Fluorouracil/Cisplatin | Journal of Clinical Oncology (ascopubs.org)
- James RD et al. Mitomycin or cisplatin chemoradiation with or without maintenance chemortherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomized, phase 3, open-label, 2x2 factorial trial. Lancet Oncol 2013; 14:516-24. Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2×2 factorial trial - The Lancet Oncology
Recurrent/Metastatic: First Line
- Rao S et al. International Rare Cancers Initiative Multicenter Randomized Phase II Trial of Cisplatin and Fluorouracil Versus Carboplatin and Paclitaxel in Advanced Anal Cancer: InterAACT. J Clin Oncol 2020; 38:2510-18. International Rare Cancers Initiative Multicenter Randomized Phase II Trial of Cisplatin and Fluorouracil Versus Carboplatin and Paclitaxel in Advanced Anal Cancer: InterAAct | Journal of Clinical Oncology (ascopubs.org)
- Mondaca S et al. FOLFCIS Treatment and Genomic Correlates of Response in Advanced Anal Squamous Cell Cancer. Clin Colorectal Cancer 2019; 18:e39-52. FOLFCIS Treatment and Genomic Correlates of Response in Advanced Anal Squamous Cell Cancer - Clinical Colorectal Cancer (clinical-colorectal-cancer.com)
- Kim S, et al. Docetaxel, cisplatin, and fluorouracil chemotherapy for metastatic or unresectable locally recurrent anal squamous cell carcinoma (Epitopes-HPV02): a multicenter, single-arm, phase 2 study. Lancet Oncol 2018; 19:1094-1106. Docetaxel, cisplatin, and fluorouracil chemotherapy for metastatic or unresectable locally recurrent anal squamous cell carcinoma (Epitopes-HPV02): a multicentre, single-arm, phase 2 study - The Lancet Oncology
- Kim S et al. DCF chemotherapy is a promising treatment for recurrent advanced squamous cell anal carcinoma. Ann Oncol 2013; 24:3045-50. DCF (docetaxel, cisplatin and 5-fluorouracil) chemotherapy is a promising treatment for recurrent advanced squamous cell anal carcinoma - Annals of Oncology
Recurrent/Metastatic: Subsequent Therapy
- Morris VK et al. Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicenter, single-arm, phase 2 study. Lancet Oncol 2017; 18:446-53. Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study - The Lancet Oncology
- Ott PA et al. Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. Ann Oncol 2017; 28:1036-41. Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal - Annals of Oncology
Biliary Tract Cancers (Gallbladder, Extrahepatic and Intrahepatic Cholangiocarcinoma) Pathways:
| Unresectable/Metastatic: First Line
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Unresectable/Metastatic: Second line
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References
Unresectable/Metastatic: First Line
- Valle J et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Eng J Med 2010; 362:1273-81.Cisplatin plus Gemcitabine versus Gemcitabine for Biliary Tract Cancer | NEJM
- Sahai V et al. Nap-paclitaxel and gemcitabine as first-line treatment of advanced or metastatic cholangiocarcinoma: a phase 2 clinical trial. JAMA Oncol 2018; 4:1707-12.Nab-Paclitaxel and Gemcitabine as First-line Treatment of Advanced or Metastatic Cholangiocarcinoma: A Phase 2 Clinical Trial | Gastroenterology | JAMA Oncology | JAMA Network
- Sharma A et al. Best supportive care compared with chemotherapy for unresectable gall bladder cancer: a randomized controlled study. Journal of Clinical Oncology 2010; 28: 4581-86.Best Supportive Care Compared With Chemotherapy for Unresectable Gall Bladder Cancer: A Randomized Controlled Study | Journal of Clinical Oncology (ascopubs.org)
- Oh D et al. Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer. NEJM Evidence June 1stst 2022.Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer (nejm.org)
- Kelley R et al. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for pateints with advanced biliarty tract cancer (KeEYNOTE-966): A randomized, double-blind, placebo-controlled, phase 3 trial. Lancet 2023; 401:1853-65.Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial - The Lancet
Unresectable/Metastatic: Second line
- Lamarca A et al. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomized, controlled trial. Lancet Oncol 2021; 22(5): 690-701.Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial - The Lancet Oncology
- Demols A et al. Regorafenib after failure of gemcitabine and platinum-based chemotherapy for locally advanced/metastatic biliary tumors: REACHIN, a randomized, double-blind, phase II trial. Ann Oncol 2020; 31: 1169-77.Regorafenib after failure of gemcitabine and platinum-based chemotherapy for locally advanced/metastatic biliary tumors: REACHIN, a randomized, double-blind, phase II trial - Annals of Oncology
- Caparica R et al. FOLFIRI as second-line treatment of metastatic biliary tract cancer patients. Autops Case Rep 2019; 9:e2019087.FOLFIRI as second-line treatment of metastatic biliary tract cancer patients - PMC (nih.gov)
- Yoo et al. Liposomal irinotecan plus fluorouracil and leucovorin versus fluorouracil and leucovorin for metastatic biliary tract cancer after progression on gemcitabine plus cisplatin (NIFTY): A multicentre, open-label, randomised, phase 2b study. Lancet Oncol 2021;22:1560–72Liposomal irinotecan plus fluorouracil and leucovorin versus fluorouracil and leucovorin for metastatic biliary tract cancer after progression on gemcitabine plus cisplatin (NIFTY): a multicentre, open-label, randomised, phase 2b study - The Lancet Oncology
- Kim RD et al. A Phase 2 Multi-institutional study of nivolumab for patients with advanced refractory biliary tract cancer. JAMA Oncol 2020; 6:888- 94.A Phase 2 Multi-institutional Study of Nivolumab for Patients With Advanced Refractory Biliary Tract Cancer | Gastroenterology | JAMA Oncology | JAMA Network
Bladder Cancer Pathways:
| Neoadjuvant/Adjuvant Therapy
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Locally Advanced Unresectable or Metastatic: First Line, Cisplatin Eligible
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Locally Advanced Unresectable or Metastatic: First Line, Cisplatin Ineligible
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Locally Advanced Unresectable or Metastatic: Second Line Post Immunotherapy and Enfortumab
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Locally Advanced Unresectable or Metastatic: Second Line Post Chemotherapy and Immunotherapy
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References
Neoadjuvant/Adjuvant Therapy:
- Sternberg CN et al. Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer Protocol no. 30924. J Clin Oncol 2001; 19:2638-46.Randomized Phase III Trial of High–Dose-Intensity Methotrexate, Vinblastine, Doxorubicin, and Cisplatin (MVAC) Chemotherapy and Recombinant Human Granulocyte Colony-Stimulating Factor Versus Classic MVAC in Advanced Urothelial Tract Tumors: European Organization for Research and Treatment of Cancer Protocol No. 30924 | Journal of Clinical Oncology (ascopubs.org)
- Von der Maase H et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol 2000; 18:3068-3077.Gemcitabine and Cisplatin Versus Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Advanced or Metastatic Bladder Cancer: Results of a Large, Randomized, Multinational, Multicenter, Phase III Study | Journal of Clinical Oncology (ascopubs.org)
- Pfister C et al. Randomized Phase III Trial of Dose-dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin, or Gemcitabine and Cisplatin as perioperative Chemotherapy for Patients with Muscle-Invasive Bladder Cancer. Annals of Oncology 2021; 32:S678.652O Dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) or gemcitabine and cisplatin (GC) as perioperative chemotherapy for patients with muscle-invasive bladder cancer (MIBC): Results of the GETUG/AFU VESPER V05 phase III trial - Annals of Oncology
- Pfister C et al. Perioperative dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin in muscle-invasive bladder cancer (VESPER): survival end points at 5 years in an open-label, randomized, phase 3 study. Lancet Oncol 2023; 25: 255-64.Perioperative dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin in muscle-invasive bladder cancer (VESPER): survival endpoints at 5 years in an open-label, randomised, phase 3 study - The Lancet Oncology
Locally Advanced Unresectable or Metastatic: First Line, Cisplatin Eligible
- Sternberg CN et al. Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer Protocol no. 30924. J Clin Oncol 2001; 19:2638-46.Randomized Phase III Trial of High–Dose-Intensity Methotrexate, Vinblastine, Doxorubicin, and Cisplatin (MVAC) Chemotherapy and Recombinant Human Granulocyte Colony-Stimulating Factor Versus Classic MVAC in Advanced Urothelial Tract Tumors: European Organization for Research and Treatment of Cancer Protocol No. 30924 | Journal of Clinical Oncology (ascopubs.org)
- Von der Maase H et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol 2000; 18:3068-77.Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study - PubMed (nih.gov)
- Powles T et al. Avelumab maintenance therapy for advanced or metastatic urothelial carcinoma. N Eng J Med 2020; 383:1218-30.Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma | NEJM
- Powles T et al. Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer. NEJM 2024; 390:875-88.Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer | New England Journal of Medicine (nejm.org)
- Van der Heijden M et al. Nivolumab plus gemcitabine-cisplatin in advanced urothelial carcinoma. NEJM 2023; 389:1778-89.Nivolumab plus Gemcitabine–Cisplatin in Advanced Urothelial Carcinoma | New England Journal of Medicine (nejm.org)
Locally Advanced Unresectable or Metastatic: First Line, Cisplatin Ineligible
- Balar AV et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm multicentre, phase 2 trial. Lancet 2017; 389:67-76Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial - The Lancet
- Grande E et al. Atezolizumab plus chemotherapy versus placebo plus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis results from a randomized, controlled, phase 3 study. Lancet Oncol 2023; 25:29-45.Atezolizumab plus chemotherapy versus placebo plus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis results from a randomised, controlled, phase 3 study - The Lancet Oncology
- Balar Av et al. First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Lancet Oncol 2017; 18:1483-92.First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study - The Lancet Oncology
- Powles T et al. Pembrolizumab alone or combined with chemotherapy versus chemotherapy as first-line therapy for advanced urothelial carcinoma (KEYNOTE-361): a randomized, open-label, phase 3 trial. Lancet Oncol 2021; 22:931-45.Pembrolizumab alone or combined with chemotherapy versus chemotherapy as first-line therapy for advanced urothelial carcinoma (KEYNOTE-361): a randomised, open-label, phase 3 trial - The Lancet Oncology
- De Santis et al. Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for Cisplatin-based chemotherapy: EORTC study 30986. J Clin Oncol 2012; 30:191-99.Randomized Phase II/III Trial Assessing Gemcitabine/Carboplatin and Methotrexate/Carboplatin/Vinblastine in Patients With Advanced Urothelial Cancer Who Are Unfit for Cisplatin-Based Chemotherapy: EORTC Study 30986 | Journal of Clinical Oncology (ascopubs.org)
- Stadler WM et al. Phase II study of single-agent gemcitabine in previously untreated patients with metastatic urothelial cancer. J Clin Oncol 1997; 15:3394-98.Phase II study of single-agent gemcitabine in previously untreated patients with metastatic urothelial cancer. | Journal of Clinical Oncology (ascopubs.org)
- Albers P et al. Randomized phase III trial of 2nd line gemcitabine and paclitaxel chemotherapy in patients with advanced bladder cancer: short-term versus prolonged treatment. Ann Oncol 2011; 22:288-94.Randomized phase III trial of 2nd line gemcitabine and paclitaxel chemotherapy in patients with advanced bladder cancer: short-term versus prolonged treatment [German Association of Urological Oncology (AUO) trial AB 20/99] - Annals of Oncology
- Siefker-Radtke AO et al. A phase 2 clinical trial of sequential neoadjuvant chemotherapy with ifosfamide, doxorubicin, and gemcitabine followed by cisplatin, gemcitabine, and ifosfamide in locally advanced urothelial cancer: final results. Cancer 2013; 119:540-47.A phase 2 clinical trial of sequential neoadjuvant chemotherapy with ifosfamide, doxorubicin, and gemcitabine followed by cisplatin, gemcitabine, and ifosfamide in locally advanced urothelial cancer - Siefker-Radtke - 2013 - Cancer - Wiley Online Library
Locally Advanced Unresectable or Metastatic: Second Line
- Bellmunt et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Eng J Med 2017; 376:1015-26.Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma | NEJM
- Sharma P et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): A multicentre, single-arm, phase 2 trial. Lancet Oncol 2017; 18:312-22.Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial - The Lancet Oncology
- Patel M et al. Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts or an open-label, phase 2 trial. Lancet Oncol 2018; 19:51-64.Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial - The Lancet Oncology
- Stadler WM et al. Phase II study of single-agent gemcitabine in previously untreated patients with metastatic urothelial cancer. J Clin Oncol 1997; 15:3394-98.Phase II study of single-agent gemcitabine in previously untreated patients with metastatic urothelial cancer. | Journal of Clinical Oncology (ascopubs.org)
- Sideris S et al. Efficacy of weekly paclitaxel treatment as a single agent chemotherapy following first-line cisplatin treatment in urothelial bladder cancer. Mol Clin Oncol 2016; 4:1063-67.Efficacy of weekly paclitaxel treatment as a single agent chemotherapy following first-line cisplatin treatment in urothelial bladder cancer - PMC (nih.gov)
- McCaffrey JA et al. Phase ii trial of docetaxel in patients with advanced or metastatic transitional-cell carcinoma. J Clin Oncol 1997; 15:1853-57.Phase II trial of docetaxel in patients with advanced or metastatic transitional-cell carcinoma. | Journal of Clinical Oncology (ascopubs.org)
- Yu E et al. Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV 201): a multicentre, single-arm, phase 2 trial. Lancet Oncol 2021; 22:872-82.Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV 201): a multicentre, single-arm, phase 2 trial - The Lancet Oncology
Breast Cancer Pathways:
| Neoadjuvant/Adjuvant: HER2 Negative
|
Neoadjuvant/Adjuvant: Triple Negative (HER2-, ER-, and PR-Negative) – 80kg or less patient
|
|
| Metastatic: HER2 Negative
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Metastatic: HER2 Positive, First Line
|
|
| Metastatic: HER2 Positive, Second Line or beyond
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Metastatic: HER2 Positive, Third Line or beyond
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Metastatic: HER2 Positive, Fourth Line or beyond
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*Use of preferred oncology medication products may be required for coverage. Refer to Cigna’s Drug and Biologic Coverage Policy 1403 for additional criteria.
§Pertuzumab, trastuzumab, and hyaluronidase-zzxf injection for subcutaneous use may be substituted for intravenous pertuzumab and intravenous trastuzumab
References
Neoadjuvant/adjuvant: HER2 negative
- Citron ML et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer. J Clin Oncol 2003; 21:1431-39.Randomized Trial of Dose-Dense Versus Conventionally Scheduled and Sequential Versus Concurrent Combination Chemotherapy as Postoperative Adjuvant Treatment of Node-Positive Primary Breast Cancer: First Report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741 | Journal of Clinical Oncology (ascopubs.org)
- Sparano JA et al. Weekly paclitaxel in adjuvant treatment of breast cancer. N Eng J Med 2008; 358:1663-71.Weekly Paclitaxel in the Adjuvant Treatment of Breast Cancer | NEJM
- Budd GT et al. SWOG S0221: a phase III Trial Comparing Chemotherapy Schedules in High-Risk Early-Stage Breast Cancer. J Clin Oncol 2015; 33(1):58-64.SWOG S0221: A Phase III Trial Comparing Chemotherapy Schedules in High-Risk Early-Stage Breast Cancer | Journal of Clinical Oncology (ascopubs.org)
- Jones S et al. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide. J Clin Oncol 2009; 27:1177-83.Docetaxel With Cyclophosphamide Is Associated With an Overall Survival Benefit Compared With Doxorubicin and Cyclophosphamide: 7-Year Follow-Up of US Oncology Research Trial 9735 | Journal of Clinical Oncology (ascopubs.org)
Neoadjuvant/Adjuvant: Triple Negative (HER2-, ER-, and PR-Negative) – 80kg or less patient
- Freshwater T, et al. Evaluation of dosing strategy for pembrolizumab for oncology indications. J Immunother Cancer. 2017;5:43. Evaluation of dosing strategy for pembrolizumab for oncology indications
- Turner DC, et al. Pembrolizumab Exposure-Response Assessments Challenged by Association of Cancer Cachexia and Catabolic Clearance. Clin Cancer Res. 2018;24(23):5841-5849. Pembrolizumab Exposure–Response Assessments Challenged by Association of Cancer Cachexia and Catabolic Clearance
- Goldstein DA, et al. Weight-Based Dosing of Pembrolizumab Every 6 Weeks in the Time of COVID-19. JAMA Oncol. 2020;6(11):1694-1695. Weight-Based Dosing of Pembrolizumab Every 6 Weeks in the Time of COVID-19
- Bryant AK, et al. Adopting Weight-Based Dosing With Pharmacy-Level Stewardship Strategies Could Reduce Cancer Drug Spending By Millions. Health Aff (Millwood). 2023;42(7):946-955. Medicare Part D Plans Greatly Increased Utilization Restrictions On Prescription Drugs, 2011–20
HER2 positive metastatic disease
- Swain et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol 2020; 21:P519-530.Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study - The Lancet Oncology
- Swain S et al. Confirmatory overall survival analysis of CLEOPATRA: a randomized, double-blind, placebo-controlled Phase III study with pertuzumab, trastuzumab, and docetaxel in patients with HER2-positive first-line metastatic breast cancer. Cancer Research 2012; 72:p5-18-26.Abstract P5-18-26: Confirmatory overall survival (OS) analysis of CLEOPATRA: a randomized, double-blind, placebo-controlled Phase III study with pertuzumab (P), trastuzumab (T), and docetaxel (D) in patients (pts) with HER2-positive first-line (1L) metastatic breast cancer (MBC) | Cancer Research | American Association for Cancer Research (aacrjournals.org)
- Bachelot T et al. Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE). Ann Oncol 2019; 30:766-773.Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE) - Annals of Oncology
- Baselga J et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Eng J Med 2012; 366: 109-119.Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer | NEJM
- Verma S et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Eng J Med 2012; 367: 1783-91.Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer | NEJM
- Modi S et al. Trastuzumab deruxtecan in previously treated HER2-positive advanced breast cancer. N Eng J Med 2020; 382:610-21.Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer | NEJM
- Cortes J et al. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Eng J Med 2022; 386:1143-54.Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer | NEJM
- Murthy RK et al. Tucatinib, trastuzumab, and capecitabine for HER-2 positive metastatic breast cancer. N Eng J Med 2020; 382:597-609.Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer | NEJM
- Blackwell KL et al. Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the EFG104900 study. J Clin Oncol 2012; 30: 2585-92.Overall Survival Benefit With Lapatinib in Combination With Trastuzumab for Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: Final Results From the EGF104900 Study | Journal of Clinical Oncology (ascopubs.org)
- Geyer C et al. Lapatinib plus capecitabine for HER2-Positive advanced breast cancer. N Eng J Med 2006; 355: 2733-43.Lapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer | NEJM
- Saura C et al. Neratinib + capecitabine versus lapatinib + capecitabine in patients with HER2+ metastatic breast cancer previously treated with ≥ HER2-directed regimens: Findings from the multinational, randomized, phase III NALA trial. J Clin Oncol 2019; 37:1002-1002.Neratinib + capecitabine versus lapatinib + capecitabine in patients with HER2+ metastatic breast cancer previously treated with ≥ 2 HER2-directed regimens: Findings from the multinational, randomized, phase III NALA trial. | Journal of Clinical Oncology (ascopubs.org)
- Rugo HS et al. Efficacy of margetuximab vs trastuzumab in patients with pretreated ERBB2-positive advanced breast cancer. JAMA Oncol 2021; 7:573-84.Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial | Breast Cancer | JAMA Oncology | JAMA Network
HER2 negative metastatic disease
- Seidman, A.D et al. Phase II Trial of Paclitaxel by 3-Hour Infusion as Initial and Salvage Chemotherapy for Metastatic Breast Cancer. J Clin Oncol 1995; 13:2575-81.Phase II trial of paclitaxel by 3-hour infusion as initial and salvage chemotherapy for metastatic breast cancer. | Journal of Clinical Oncology (ascopubs.org)
- Perez, E.A et al. Multicenter Phase II Trial of Weekly Paclitaxel in Women with Metastatic Breast Cancer. J Clin Oncol 2001; 19:4216-23.Multicenter Phase II Trial of Weekly Paclitaxel in Women With Metastatic Breast Cancer | Journal of Clinical Oncology (ascopubs.org)
- Burris HA, 3rd. Single-agent docetaxel (Taxotere) in randomized phase III trials. Semin Oncol 1999; 26:1-6.Single-agent docetaxel (Taxotere) in randomized phase III trials - PubMed (nih.gov)
- Harvey V et al. Phase III trial comparing three doses of docetaxel for second-line treatment of advanced breast cancer. J Clin Oncol. 2006; 24:4963-70.Phase III Trial Comparing Three Doses of Docetaxel for Second-Line Treatment of Advanced Breast Cancer | Journal of Clinical Oncology (ascopubs.org)
- Rivera E et al. Phase 3 study comparing the use of docetaxel on an every-3-week versus weekly schedule in the treatment of metastatic breast cancer. Cancer. 2008; 112:1455-61.Phase 3 study comparing the use of docetaxel on an every 3 week versus weekly schedule in the treatment of metastatic breast cancer - Rivera - 2008 - Cancer - Wiley Online Library
- Chan S et al. Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. J Clin Oncol 1999; 17:2341-54.Prospective Randomized Trial of Docetaxel Versus Doxorubicin in Patients With Metastatic Breast Cancer | Journal of Clinical Oncology (ascopubs.org)
- Gasparini G et al. Weekly epirubicin versus doxorubicin as second line therapy in advanced breast cancer. A randomized clinical trial. Am J Clin Oncol 1991; 14:38-44.Weekly epirubicin versus doxorubicin as second line therapy in advanced breast cancer. A randomized clinical trial - PubMed (nih.gov)
- O’Brien ME et al. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCL versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol 2004; 15:440-49.Reduced cardiotoxicity and comparable efficacy in a phase IIItrial of pegylated liposomal doxorubicin HCl(CAELYX™/Doxil®) versus conventional doxorubicin forfirst-line treatment of metastatic breast cancer - Annals of Oncology
- Seidman AD. Gemcitabine as single-agent therapy in the management of advanced breast cancer. Oncology. 2001; 15:11-14.Gemcitabine as Single-Agent Therapy in the Management of Advanced Breast Cancer (cancernetwork.com)
- Zelek L et al. Weekly vinorelbine is an effective palliative regimen after failure with anthracyclines and taxanes in metastatic breast carcinoma. Cancer. 2001; 92:2267-72.Weekly vinorelbine is an effective palliative regimen after failure with anthracyclines and taxanes in metastatic breast carcinoma - PubMed (nih.gov)
- Bajetta E et al. Safety and efficacy of two different doses of capecitabine in the treatment of advanced breast cancer in older women. J Clin Oncol. 2005; 23:2155-61.Safety and Efficacy of Two Different Doses of Capecitabine in the Treatment of Advanced Breast Cancer in Older Women | Journal of Clinical Oncology (ascopubs.org)
- Gradishar WJ et al. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol. 2005; 23:7794-803.Phase III Trial of Nanoparticle Albumin-Bound Paclitaxel Compared With Polyethylated Castor Oil–Based Paclitaxel in Women With Breast Cancer | Journal of Clinical Oncology (ascopubs.org)
- Perez EA et al. Efficacy and safety of ixabepilone (BMS-247550) in a phase II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. J Clin Oncol. 2007; 25:3407-14.Efficacy and Safety of Ixabepilone (BMS-247550) in a Phase II Study of Patients With Advanced Breast Cancer Resistant to an Anthracycline, a Taxane, and Capecitabine | Journal of Clinical Oncology (ascopubs.org)
- Cortes J et al. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet. 2011; 377:914-23.Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study - The Lancet
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Pathways:
| First Line : WITHOUT del (17P)/TP53 Mutation
|
First Line : WITH del (17P)/TP53 Mutation
|
*Use of preferred oncology medication products may be required for coverage. Refer to Cigna’s Drug and Biologic Coverage Policy 1403 for additional criteria.
References
First line with or without del (17p)/TP53 mutation
- Burger JA et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Eng J Med 2015; 373:2425-37.Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia | NEJM
- Burger JA et al. Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study. Leukemia. 2020; 34:787-98.Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study | Leukemia (nature.com)
- Fischer K et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Eng J Med 2019; 380:2225-36.Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions | NEJM
- Al-Sawaf O et al. Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2020; 21:1188-200.Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial - The Lancet Oncology
- Awan FT et al. Acalabrutinib monotherapy in patients with chronic lymphocytic leukemia who are intolerant to ibrutinib. Blood Adv. 2019; 3:1553-62.Acalabrutinib monotherapy in patients with chronic lymphocytic leukemia who are intolerant to ibrutinib | Blood Advances | American Society of Hematology (ashpublications.org)
- Sharman JP et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Lancet. 2020; 395:1278- 91.Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab for treatment-naive chronic lymphocytic leukaemia (ELEVATE-TN): a randomised, controlled, phase 3 trial - The Lancet
- Tam C, et al. Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Lancet Oncol 2022;23:1031-1043.Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial - The Lancet Oncology
- Sharman J et al. Phase 2, multicenter GIBB study of obinutuzumab plus bendamustine in previously untreated patients with chronic lymphocytic leukemia. Leukemia & Lymphoma 2020; 62:791-800.Full article: Phase 2, multicenter GIBB study of obinutuzumab plus bendamustine in previously untreated patients with chronic lymphocytic leukemia (tandfonline.com
- Michallet A et al. Rituximab plus bendamustine or chlorambucil for chronic lymphocytic leukemia: primary analysis of the randomized, open-label MABLE study. Haematologica 2018; 103:698-706.Rituximab plus bendamustine or chlorambucil for chronic lymphocytic leukemia: primary analysis of the randomized, open-label MABLE study | Haematologica
- Moreno C et al. Ibrutinib plus Obinutuzumab versus cholarmbucil plus Obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomized, open-label, phase 3 trial. Lancet Onco 2019; 20:43-56.Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial - The Lancet Oncology
- Shanafelt T et al. Ibrutinib-Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia. NEJM 2019; 381:432-43.Ibrutinib–Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia | New England Journal of Medicine (nejm.org)
- Wierda W et al. Ibrutinib Plus Venetoclax for First-Line Treatment of Chronic Lymphocytic Leukemia: Primary Analysis Results From the Minimal Residual Disease Cohort of the Randomized Phase II CAPTIVATE study. JCO 2021; 39:3853-65.Ibrutinib Plus Venetoclax for First-Line Treatment of Chronic Lymphocytic Leukemia: Primary Analysis Results From the Minimal Residual Disease Cohort of the Randomized Phase II CAPTIVATE Study | Journal of Clinical Oncology (ascopubs.org)
- Brown J.R. et al. Fixed-Duration Acalabrutinib Combinations in Untreated Chronic Lymphocytic Leukemia. N Eng J Med 2025;392:748-62. Fixed-Duration Acalabrutinib Combinations in Untreated Chronic Lymphocytic Leukemia | New England Journal of Medicine
Colorectal Cancer Pathways:
| Subsequent Therapy with a VEGF Inhibitor
|
Metastatic Disease: dMMR/MSI-H or POLE/POLD1 Mutation
|
*Use of preferred oncology medication products may be required for coverage. Refer to Cigna’s Drug and Biologic Coverage Policy 1403 for additional criteria.
References
Subsequent Therapy with a VEGF Inhibitor
- Bennouna J et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol. 2013; 14:29-37.Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial - The Lancet Oncology
- Tabernero J et al. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Lancet Oncol. 2015; 16:499-508.Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study - The Lancet Oncology
- Tabernero J et al. Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial. Eur J Cancer. 2014; 50:320-31.Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: Prespecified subgroup analyses from the VELOUR trial - European Journal of Cancer (ejcancer.com)
Metastatic disease: dMMR/MSI-H or POLE/POLD1 mutation
- Andre T et al. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. NEJM 2020: 383;2207-18.Pembrolizumab in Microsatellite-Instability–High Advanced Colorectal Cancer | New England Journal of Medicine (nejm.org)
- Lenz, HJ et al. First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase II CheckMate 142 Study. JCO 2022; 40:161-70.First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase II CheckMate 142 Study | Journal of Clinical Oncology (ascopubs.org)
Diffuse Large B-Cell Lymphoma Pathways:
| Second Line Therapy, Relapsed Disease >12 Months, Intention to Proceed to Transplant
|
Second Line Therapy, Relapsed Disease >12 Months, No Intention to Proceed to Transplant or CAR T
|
*Use of preferred oncology medication products may be required for coverage. Refer to Cigna’s Drug and Biologic Coverage Policy 1403 or additional criteria.
References
Second line therapy, relapsed disease >12 months, no intention to proceed to transplant or CART.
- Lopez A et al. GEMOX-R regimen is a highly effective salvage regimen in patients with refractory/relapsing diffuse large-cell lymphoma: a phase II study. Eur J Haematol. 2008; 80:127-32.GEMOX-R regimen is a highly effective salvage regimen in patients with refractory/relapsing diffuse large-cell lymphoma: a phase II study - López - 2008 - European Journal of Haematology - Wiley Online Library
- Gopal AK et al. Efficacy and safety of gemcitabine, carboplatin, dexamethasone, and rituximab in patients with relapsed/refractory lymphoma: a prospective multi-center phase II study by the Puget Sound Oncology Consortium. Leuk Lymphoma. 2010; 51:1523-9.Efficacy and safety of gemcitabine, carboplatin, dexamethasone, and rituximab in patients with relapsed/refractory lymphoma: a prospective multi-center phase II study by the Puget Sound Oncology Consortium: Leukemia & Lymphoma: Vol 51, No 8 (tandfonline.com)
- Sehn LH et al. Polatuzumab vedotin in relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. 2020; 38:155-65Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma | Journal of Clinical Oncology (ascopubs.org)
- Salles G et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020; 21:978-88.Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study - The Lancet Oncology
- Abramson J et al. Glofitamab plus gemcitabine and oxaliplatin (GemOx) versus rituximab-GemOx for replapsed or refractory diffuse large B-cell lymphoma (STARGLO): a global phase 3, randomized, open-label trial. The Lancet. 2024;404:1940-54.Glofitamab plus gemcitabine and oxaliplatin (GemOx) versus rituximab-GemOx for relapsed or refractory diffuse large B-cell lymphoma (STARGLO): a global phase 3, randomised, open-label trial - The Lancet
Second line therapy, relapsed disease >12 months, intention to proceed to transplant.
- Kewalramani T et al. Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma. Blood. 2004; 103:3684-8.Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma | Blood | American Society of Hematology (ashpublications.org)
- Crump M et al. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014; 32:3490-6.Randomized Comparison of Gemcitabine, Dexamethasone, and Cisplatin Versus Dexamethasone, Cytarabine, and Cisplatin Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed and Refractory Aggressive Lymphomas: NCIC-CTG LY.12 | Journal of Clinical Oncology (ascopubs.org)
- Velasquez WS et al. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood. 1988; 71:117-22.Effective Salvage Therapy for Lymphoma With Cisplatin in Combination With High-Dose Ara-C and Dexamethasone (DHAP) - ScienceDirect
- Velasquez WS et al. ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol. 1994; 12:1169-76.ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. | Journal of Clinical Oncology (ascopubs.org)
- Lignon J, et al. Rituximab, dexamethasone, cytarabine, and oxaliplatin (R-DHAX) is an effective and safe salvage regimen in relapsed/refractory B-cell non-Hodgkin lymphoma. Clin Lymphoma Myeloma Leuk. 2010; 10:262-9.Rituximab, Dexamethasone, Cytarabine, and Oxaliplatin (R-DHAX) Is an Effective and Safe Salvage Regimen in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma - Clinical Lymphoma, Myeloma and Leukemia (clinical-lymphoma-myeloma-leukemia.com)
- Rigacci L et al. Oxaliplatin-based chemotherapy (dexamethasone, high-dose cytarabine, and oxaliplatin)+/-rituximab is an effective salvage regimen in patients with relapsed or refractory lymphoma. Cancer. 2010; 116:4573-9.Oxaliplatin-based chemotherapy (dexamethasone, high-dose cytarabine, and oxaliplatin) ± rituximab is an effective salvage regimen in patients with relapsed or refractory lymphoma - Rigacci - 2010 - Cancer - Wiley Online Library
Endometrial Cancer Pathways:
| Recurrent/Metastatic: First Line and Subsequent Therapy
|
*Use of preferred oncology medication products may be required for coverage. Refer to Cigna’s Drug and Biologic Coverage Policy 1403 for additional criteria.
References
Recurrent/Metastatic: First Line and Subsequent Therapy
- Miller DS et al. Carboplatin and paclitaxel for advanced endometrial cancer: final overall survival and adverse event analysis of a phase III trial (NRG Oncology/GOG0209). J Clin Oncol. 2020; 38:3841-50.Carboplatin and Paclitaxel for Advanced Endometrial Cancer: Final Overall Survival and Adverse Event Analysis of a Phase III Trial (NRG Oncology/GOG0209) | Journal of Clinical Oncology (ascopubs.org)
- Secord AA et al. Weekly low-dose paclitaxel and carboplatin in the treatment of advanced or recurrent cervical and endometrial cancer. Int J Clin Oncol. 2007; 12:31-6.Weekly low-dose paclitaxel and carboplatin in the treatment of advanced or recurrent cervical and endometrial cancer | SpringerLink
- Fleming GF et al. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2004; 22:2159-66.Phase III Trial of Doxorubicin Plus Cisplatin With or Without Paclitaxel Plus Filgrastim in Advanced Endometrial Carcinoma: A Gynecologic Oncology Group Study | Journal of Clinical Oncology (ascopubs.org)
- Cella D et al. Patient-reported peripheral neuropathy of doxorubicin and cisplatin with and without paclitaxel in the treatment of advanced endometrial cancer: results from GOG 184. Gynecol Oncol. 2010; 119:538-42.Patient-reported peripheral neuropathy of doxorubicin and cisplatin with and without paclitaxel in the treatment of advanced endometrial cancer: Results from GOG 184 - Gynecologic Oncology (gynecologiconcology-online.net)
- Fader AN et al. Randomized phase II trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-trastuzumab in uterine serous carcinomas that overexpress human epidermal growth factor receptor 2/neu. J Clin Oncol. 2018; 36:2044-51.Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu | Journal of Clinical Oncology (ascopubs.org)
- Lorusso D et al. Carboplatin-paclitaxel compared to carboplatin-paclitaxel-bevacizumab in advanced or recurrent endometrial cancer: MITO END-2 - a randomized phase II trial. Gynecol Oncol. 2019; 155:406-12.Carboplatin-paclitaxel compared to Carboplatin-Paclitaxel-Bevacizumab in advanced or recurrent endometrial cancer: MITO END-2 - A randomized phase II trial - Gynecologic Oncology (gynecologiconcology-online.net)
- Nomura H et al. Randomized phase II study comparing docetaxel plus cisplatin, docetaxel plus carboplatin, and paclitaxel plus carboplatin in patients with advanced or recurrent endometrial carcinoma: a Japanese Gynecologic Oncology Group study (JGOG2041). Ann Oncol. 2011; 22:636-42.Randomized phase II study comparing docetaxel plus cisplatin, docetaxel plus carboplatin, and paclitaxel plus carboplatin in patients with advanced or recurrent endometrial carcinoma: a Japanese Gynecologic Oncology Group study (JGOG2041) - Annals of Oncology
- Lissoni A et al. Phase II study of paclitaxel as salvage treatment in advanced endometrial cancer. Ann Oncol. 1996; 7:861-3.Phase II study of paclitaxel as salvage treatment in advanced endometrial cancer (annalsofoncology.org)
- Thigpen JT et al. A randomized comparison of doxorubicin alone versus doxorubicin plus cyclophosphamide in the management of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1994; 12:1408-14.A randomized comparison of doxorubicin alone versus doxorubicin plus cyclophosphamide in the management of advanced or recurrent endometrial carcinoma: A Gynecologic Oncology Group study. | Journal of Clinical Oncology (ascopubs.org)
- Wadler S et al. Topotecan is an active agent in the first-line treatment of metastatic or recurrent endometrial carcinoma: Eastern Cooperative Oncology Group study E3E93. J Clin Oncol. 2003; 21:2110-4.Topotecan Is an Active Agent in the First-Line Treatment of Metastatic or Recurrent Endometrial Carcinoma: Eastern Cooperative Oncology Group Study E3E93 | Journal of Clinical Oncology (ascopubs.org)
- Seski JC et al. Cisplatin chemotherapy for disseminated endometrial cancer. Obstet Gynecol. 1982; 59:225-8.Cisplatin chemotherapy for disseminated endometrial cancer - PubMed (nih.gov)
- Van Wijk FH et al. Phase II study of carboplatin in patients with advanced or recurrent endometrial carcinoma. a trial of the EORTC Gynaecological Cancer Group. Eur J Cancer. 2003; 39:78-85.Phase II study of carboplatin in patients with advanced or recurrent endometrial carcinoma. A trial of the EORTC Gynaecological Cancer Group - European Journal of Cancer (ejcancer.com)
- Aghajanian et al. Phase II trial of bevacizumab in recurrent or persistent endometrial cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2011; 29:2259-65.Phase II Trial of Bevacizumab in Recurrent or Persistent Endometrial Cancer: A Gynecologic Oncology Group Study | Journal of Clinical Oncology (ascopubs.org)
- Muggia FM et al. Phase II trial of the pegylated liposomal doxorubicin in previously treated metastatic endometrial cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2002; 20:2360-4.Phase II Trial of the Pegylated Liposomal Doxorubicin in Previously Treated Metastatic Endometrial Cancer: A Gynecologic Oncology Group Study | Journal of Clinical Oncology (ascopubs.org)
- Oza AM et al. Phase II study of temsirolimus in women with recurrent or metastatic endometrial cancer: a trial of the NCIC Clinical Trials group. J Clin Oncol. 2011; 29:3278-85.Phase II Study of Temsirolimus in Women With Recurrent or Metastatic Endometrial Cancer: A Trial of the NCIC Clinical Trials Group | Journal of Clinical Oncology (ascopubs.org)
- Katsumata N et al. Phase II trial of docetaxel in advanced or metastatic endometrial cancer: a Japanese Cooperative study. British Journal of Cancer. 2005; 93:999-1004.Phase II trial of docetaxel in advanced or metastatic endometrial cancer: a Japanese Cooperative Study - PMC (nih.gov)
Esophageal and Esophagogastric Junction Cancer Pathways:
| Unresectable/Recurrent/Metastatic: First Line, Adenocarcinoma, HER2 Negative, MSS
|
Unresectable/Recurrent/Metastatic: First Line, Squamous Cell, MSS
|
Unresectable/Recurrent/Metastatic: Subsequent Therapy, Adenocarcinoma or Squamous Cell
|
References
Unresectable/Recurrent/Metastatic: First Line, adenocarcinoma, HER2 Negative, MSS
- Al-Batran SE et al. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008; 26:1435-42.Phase III Trial in Metastatic Gastroesophageal Adenocarcinoma with Fluorouracil, Leucovorin Plus Either Oxaliplatin or Cisplatin: A Study of the Arbeitsgemeinschaft Internistische Onkologie | Journal of Clinical Oncology (ascopubs.org)
- Van Meerten E et al. First-line treatment with oxaliplatin and capecitabine in patients with advanced or metastatic oesophageal cancer: a phase II study. British Journal of Cancer. 2007; 96:1348-52.First-line treatment with oxaliplatin and capecitabine in patients with advanced or metastatic oesophageal cancer: a phase II study | British Journal of Cancer (nature.com)
- Cunningham D et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Eng J Med 2008; 358:36-46.Capecitabine and Oxaliplatin for Advanced Esophagogastric Cancer | NEJM
- Kim GM et al. A randomized phase II trial of S-1-oxaliplatin versus capecitabine-oxaliplatin in advanced gastric cancer. Eur J Cancer. 2012; 48:518-26.A randomized phase II trial of S-1-oxaliplatin versus capecitabine–oxaliplatin in advanced gastric cancer - European Journal of Cancer (ejcancer.com)
- Dank M et al. Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2008; 19:1450-7.Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction - Annals of Oncology
- Janjigian YY et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastrooesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021; 398:27-40.First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial - The Lancet
- Sun JM et al. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021; 398:759-71.Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study - The Lancet
- Qiu MZ, et al. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial. BMJ. 2024;385:e078876. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial
Unresectable/Recurrent/Metastatic: First Line, squamous cell, MSS
- Lorenzen S et al. Cetuximab plus cisplatin-5-fluorouracil versus cisplatin-5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase II study of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2009; 20:1667-73.Cetuximab plus cisplatin–5-fluorouracil versus cisplatin–5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase II study of the Arbeitsgemeinschaft Internistische Onkologie - Annals of Oncology
- Lee SJ et al. Capecitabine in combination with either cisplatin or weekly paclitaxel as a first-line treatment for metastatic esophageal squamous cell carcinoma: a randomized phase II study. BMC Cancer. 2015; 15:693.Capecitabine in combination with either cisplatin or weekly paclitaxel as a first-line treatment for metastatic esophageal squamous cell carcinoma: a randomized phase II study | BMC Cancer | Full Text (biomedcentral.com)
- Sun JM et al. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021; 398:759-71.Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study - The Lancet
- Doki Y et al. Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma. N Engl J Med 2022; 386:449-62.Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma | NEJM
- Kato K, et al. First-line nivolumab plus ipilimumab or chemotherapy versus chemotherapy alone in advanced esophageal squamous cell carcinoma: a Japanese subgroup analysis of open-label, phase 3 trial (CheckMate 648/ONO-4538-50). Esophagus. 2023;20(2):291-301. First-line nivolumab plus ipilimumab or chemotherapy versus chemotherapy alone in advanced esophageal squamous cell carcinoma: a Japanese subgroup analysis of open-label, phase 3 trial (CheckMate 648/ONO-4538-50)
- Xu J, et al. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (RATIONALE-306): a global, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2023;24(5):483-495. Erratum in: Lancet Oncol. 2024;25(3):e102. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (RATIONALE-306): a global, randomised, placebo-controlled, phase 3 study
Unresectable/Recurrent/Metastatic: Subsequent Therapy, adenocarcinoma or squamous cell
- Hironaka S et al. Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol. 2013; 31:4438-44.Randomized, Open-Label, Phase III Study Comparing Irinotecan With Paclitaxel in Patients With Advanced Gastric Cancer Without Severe Peritoneal Metastasis After Failure of Prior Combination Chemotherapy Using Fluoropyrimidine Plus Platinum: WJOG 4007 Trial | Journal of Clinical Oncology (ascopubs.org)
- Ilson DH et al. Paclitaxel given by a weekly 1-h infusion in advanced esophageal cancer. Ann Oncol. 2007; 18:898-902.Paclitaxel given by a weekly 1-h infusion in advanced esophageal cancer - Annals of Oncology
- Muro K et al. A phase II study of single-agent docetaxel in patients with metastatic esophageal cancer. Ann Oncol. 2004; 15:955-9.A phase II study of single-agent docetaxel in patients with metastatic esophageal cancer - Annals of Oncology
- Ford HE et al. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014; 15:78-86.Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial - The Lancet Oncology
- Mizota et al. A retrospective comparison of docetaxel and paclitaxel for patients with advanced or recurrent esophageal cancer who previously received platinum-based chemotherapy. Oncology. 2011; 81:237-42.A Retrospective Comparison of Docetaxel and Paclitaxel for Patients with Advanced or Recurrent Esophageal Cancer Who Previously Received Platinum-Based Chemotherapy - Abstract - Oncology 2011, Vol. 81, No. 3-4 - Karger Publishers
- Thuss-Patience PC et al. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer. 2011; 47:2306-14.Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer – A randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO) - European Journal of Cancer (ejcancer.com)
- Wilke H et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014; 15:1224-35.Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial - The Lancet Oncology
- Marabelle A et al. Efficacy of Pembrolizumab in Patients with Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol. 2020; 38:1-10.Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair–Deficient Cancer: Results From the Phase II KEYNOTE-158 Study | Journal of Clinical Oncology (ascopubs.org)
- Shitara K et al. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018; 19:1437-48.Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial - The Lancet Oncology
- Fuchs CS et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014; 383:31-9.Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial - The Lancet
- Kojima T et al. Randomized phase III KEYNOTE-181 study of pembrolizumab versus chemotherapy in advanced esophageal cancer. J Clin Oncol. 2020; 38:4138-48.Randomized Phase III KEYNOTE-181 Study of Pembrolizumab Versus Chemotherapy in Advanced Esophageal Cancer | Journal of Clinical Oncology (ascopubs.org)
- Kato K et al. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019; 20:1506-1517.Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial - The Lancet Oncology
Follicular B-Cell Lymphoma Pathways:
| Grade 1-2 Disease: First Line
|
*Use of preferred oncology medication products may be required for coverage. Refer to Cigna’s Drug and Biologic Coverage Policy 1403 for additional criteria.
References
Grade 1-2 Disease: First Line
- Hiddemann W et al. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018; 36:2395-404.Immunochemotherapy With Obinutuzumab or Rituximab for Previously Untreated Follicular Lymphoma in the GALLIUM Study: Influence of Chemotherapy on Efficacy and Safety | Journal of Clinical Oncology (ascopubs.org)
- Czuczman MS et al. Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol. 1999; 17:268-76. Treatment of Patients With Low-Grade B-Cell Lymphoma With the Combination of Chimeric Anti-CD20 Monoclonal Antibody and CHOP Chemotherapy | Journal of Clinical Oncology (ascopubs.org)
- Hiddemann W et al. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005; 106:3725-32.Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group | Blood | American Society of Hematology (ashpublications.org)
- Rummel MJ et al. Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet. 2013; 381:1203- 10.Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial - The Lancet
- Flinn IW et al. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014; 123:2944-52.Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study | Blood | American Society of Hematology (ashpublications.org)
- Marcus R et al. Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol. 2008; 26:4579-86Phase III Study of R-CVP Compared With Cyclophosphamide, Vincristine, and Prednisone Alone in Patients With Previously Untreated Advanced Follicular Lymphoma | Journal of Clinical Oncology (ascopubs.org)
- Morschhauser F et al. Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma. N Engl J Med 2018; 379:934-47.Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma | NEJM
- Morschhauser F et al. Six-Year Results From RELEVANCE: Lenalidomide Plus Rituximab (R2) Versus Rituximab-Chemotherapy Followed by Rituximab Maintenance in Untreated Advanced Follicular Lymphoma. J Clin Oncol 2022; 40:3239-45.Six-Year Results From RELEVANCE: Lenalidomide Plus Rituximab (R2) Versus Rituximab-Chemotherapy Followed by Rituximab Maintenance in Untreated Advanced Follicular Lymphoma | Journal of Clinical Oncology (ascopubs.org)
- Bachy E et al. Obinutuzumab plus lenalidomide (GALEN) in advanced, previously untreated follicular lymphoma in need of systemic therapy. Blood 2022; 139:2338-46Obinutuzumab plus lenalidomide in advanced, previously untreated follicular lymphoma in need of systemic therapy: a LYSA study | Blood | American Society of Hematology (ashpublications.org)
Head and Neck Cancer Pathways:
| Advanced Disease: Definitive Chemoradiation
|
References
Advanced Disease: Definitive Chemoradiation
- Bernier J, Domenge C, Ozsahin M, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004; 350:1945-52.Postoperative Irradiation with or without Concomitant Chemotherapy for Locally Advanced Head and Neck Cancer | NEJM
- Chitapanarux I et al. Chemoradiation comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: randomised, non-inferiority, open trial. Eur J Cancer. 2007; 43:1399-406.Chemoradiation comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: Randomised, non-inferiority, open trial - European Journal of Cancer (ejcancer.com)
- Kiyota N et al. Phase II/III trial of post-operative chemoradiotherapy comparing 3-weekly cisplatin with weekly cisplatin in high-risk patients with squamous cell carcinoma of head and neck (JCOG1008). J Clin Oncol. 2020; 38:abstract 6502Phase II/III trial of post-operative chemoradiotherapy comparing 3-weekly cisplatin with weekly cisplatin in high-risk patients with squamous cell carcinoma of head and neck (JCOG1008). | Journal of Clinical Oncology (ascopubs.org)
- Clark JI et al. Phase II evaluation of paclitaxel in combination with carboplatin in advanced head and neck carcinoma. Cancer. 2001; 92:2334-40.Phase II evaluation of paclitaxel in combination with carboplatin in advanced head and neck carcinoma - PubMed (nih.gov)
- Gebre-Medhin M et al. ARTSCAN III: A Randomized Phase III Study Comparing Chemoradiotherapy With Cisplatin Versus Cetuximab in Patients With Locoregionally Advanced Head and Neck Squamous Cell Cancer. J Clin Oncol. 2021; 39:38-47.ARTSCAN III: A Randomized Phase III Study Comparing Chemoradiotherapy With Cisplatin Versus Cetuximab in Patients With Locoregionally Advanced Head and Neck Squamous Cell Cancer | Journal of Clinical Oncology (ascopubs.org)
Hepatocellular Carcinoma Pathways:
| Metastatic or Unresectable Disease: First Line
|
Metastatic or Unresectable Disease: Subsequent Therapy
|
*Use of preferred oncology medication products may be required for coverage. Refer to Cigna’s Drug and Biologic Coverage Policy 1403 for additional criteria.
References
Metastatic or Unresectable Disease: First line
- Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Eng J Med 2008; 359:378-90.Sorafenib in Advanced Hepatocellular Carcinoma | NEJM
- Kudo M et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018; 391:1163-73.Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial - The Lancet
- Finn RS et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Eng J Med 2020; 382:1894- 905.Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma | NEJM
- Yau T et al. CheckMate 459: a randomized, multi-center phase III study of nivolumab (NIVO) vs sorafenib (SOR) as first-line treatment in patients with advanced hepatocellular carcinoma (aHCC). Ann Oncol. 2019; 30:v874-v5.CheckMate 459: A randomized, multi-center phase III study of nivolumab (NIVO) vs sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC) - ScienceDirect
- Abou-Alfa G et al. Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma. NEJM EVID 2022; 1.Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma | NEJM Evidence
- Zhu A et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomized, open-label phase 2 trial. Lancet Onco 2018; 19:940-52.Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial - The Lancet Oncology
- Yau T, et al. Nivolumab plus ipilimumab versus lenvatinib or sorafenib as first-line treatment for unresectable hepatocellular carcinoma (CheckMate 9DW): an open-label, randomised, phase 3 trial. Lancet. 2025;405(10492):1851-1864. Nivolumab plus ipilimumab versus lenvatinib or sorafenib as first-line treatment for unresectable hepatocellular carcinoma (CheckMate 9DW): an open-label, randomised, phase 3 trial
- Qin S, et al. Tislelizumab vs Sorafenib as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2023;9(12):1651-1659. Quantification of Treatment Effect of Tislelizumab vs Sorafenib for Hepatocellular Carcinoma—Reply
Metastatic or Unresectable Disease: Subsequent therapy
- Bruix J et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017; 389:56-66.References in Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial - The Lancet
- Abou-Alfa GK et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Eng J Med 2018; 379:54-63.Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma | NEJM
- Zhu AX et al. REACH-2: a randomized, double-blind, placebo-controlled phase 3 study of ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma (HCC) and elevated baseline alpha-fetoprotein (AFP) following firstline sorafenib. J Clin Oncol. 2018; 36: abstract 4003.REACH-2: A randomized, double-blind, placebo-controlled phase 3 study of ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma (HCC) and elevated baseline alpha-fetoprotein (AFP) following first-line sorafenib. | Journal of Clinical Oncology (ascopubs.org)
- Crocenzi TS et al. Nivolumab (nivo) in sorafenib (sor)-naive and-experienced pts with advanced hepatocellular carcinoma (HCC): CheckMate 040 study. J Clin Oncol. 2017; 35: abstract 4013.Nivolumab (nivo) in sorafenib (sor)-naive and -experienced pts with advanced hepatocellular carcinoma (HCC): CheckMate 040 study. | Journal of Clinical Oncology (ascopubs.org)
- Qin S et al. Pembrolizumab plus best supportive care versus placebo plus best supportive care as second-line therapy in patients in Asia with advanced hepatocellular carcinoma (HCC): Phase 3 KEYNOTE-394 study. JCO 2022; 40:383-383.Pembrolizumab plus best supportive care versus placebo plus best supportive care as second-line therapy in patients in Asia with advanced hepatocellular carcinoma (HCC): Phase 3 KEYNOTE-394 study. | Journal of Clinical Oncology (ascopubs.org)
Hodgkin Lymphoma Pathways:
| Stage III/IV Classical Hodgkin Lymphoma - Ages 18-60 years old
|
References
Stage III/IV Classical Hodgkin Lymphoma – Ages 18-60 years old
- Gordon LI et al. Randomized phase III trial of ABVD versus Stanford V with or without radiation therapy in locally extensive and advanced-stage Hodgkin lymphoma: an intergroup study coordinated by the Eastern Cooperative Oncology Group (E2496). J Clin Oncol. 2013; 31:684-91.Randomized Phase III Trial of ABVD Versus Stanford V With or Without Radiation Therapy in Locally Extensive and Advanced-Stage Hodgkin Lymphoma: An Intergroup Study Coordinated by the Eastern Cooperative Oncology Group (E2496) | Journal of Clinical Oncology (ascopubs.org)
- Johnson P et al. Adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma. N Eng J Med 2016; 1:2419-29.Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin’s Lymphoma | NEJM
- Straus et al. Brentuximab vedotin with chemotherapy for stage III/IV classical Hodgkin lymphoma: 3-year update of the ECHELON-1 study. Blood. 2020; 135:735-42.Brentuximab vedotin with chemotherapy for stage III/IV classical Hodgkin lymphoma: 3-year update of the ECHELON-1 study | Blood | American Society of Hematology (ashpublications.org)
- Nivolumab+AVD in Advanced-Stage Classic Hodgkin’s Lymphoma. N Eng J Med 2024; 391:1379-89. Nivolumab+AVD in Advanced-Stage Classic Hodgkin’s Lymphoma | New England Journal of Medicine
- Borchmann P et al. Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): a randomized, multicentre, parallel, open-label, phase 3 trial. The Lancet 2024; 404:341-52.Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): a randomised, multicentre, parallel, open-label, phase 3 trial - The Lancet
Kidney Cancer Pathways:
| Clear Cell, First Line: Favorable risk
|
References
Clear Cell, First Line: Favorable risk
- Motzer RJ et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Eng J Med 2013; 1:722-31.Pazopanib versus Sunitinib in Metastatic Renal-Cell Carcinoma | NEJM
- Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Eng J Med 2018; 378:1277-129021.Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma | NEJM
- Motzer RJ et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Eng J Med 2019; 380:1103-15.Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma | NEJM
- Motzer RJ et al. Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. N Eng J Med 2021; 384:1289-1300.Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma | NEJM
- Choueiri TK et al. Nivolumab + cabozantinib vs sunitinib in first-line treatment for advanced renal cell carcinoma: First results from the randomized phase III CheckMate 9ER trial. Ann Oncol. 2020; 31:S1159.696O_PR Nivolumab + cabozantinib vs sunitinib in first-line treatment for advanced renal cell carcinoma: First results from the randomized phase III CheckMate 9ER trial - Annals of Oncology
- Rini BI et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Eng J Med 2019; 380:1116-27.Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma | NEJM
- Choueiri TK, et al. Nivolumab plus ipilimumab vs sunitinib for first-line treatment of advanced renal cell carcinoma: Final analysis from the phase 3 CheckMate 214 trial. J Clin Oncol. 2025;43:4505. Nivolumab plus ipilimumab vs sunitinib for first-line treatment of advanced renal cell carcinoma: Final analysis from the phase 3 CheckMate 214 trial.
Lung Cancer: Non-Small Cell Lung Cancer Pathways:
| Metastatic: First Line, EGFR Exon 19 Deletion or Exon 21 L858R Mutations
|
|
| Metastatic: First Line, Nonsquamous, PD-L1 ≥ 50%, No Actionable Mutations
|
Metastatic: First Line, Squamous, PD-L1 ≥ 50%, No Actionable Mutations
|
| Metastatic: First Line, Nonsquamous, PD-L1 TPS <50%, No Driver Mutation
|
Metastatic: First Line, Squamous, PD-L1 TPS<50%, No Driver Mutation
|
| Metastatic: Subsequent Therapy, Nonsquamous, No Actionable Mutations
|
Metastatic: Subsequent Therapy, Squamous, No Actionable Mutations
|
References
Metastatic: First line, squamous or nonsquamous, PD-L1 ≥ 50%, no actionable mutations
- Reck M et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Eng J Med 2016; 375:1823-33.Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer | NEJM
- Reck M et al. Five-year outcomes with pembrolizumab versus chemotherapy for metastatic non-small-cell lung cancer with PD-L1 tumor proportion score >= 50. J Clin Oncol. 2021; 39:2339-49.Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non–Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50% | Journal of Clinical Oncology (ascopubs.org)
- Herbst RS et al. Atezolizumab for First-Line Treatment of PD-L1-Selected Patients with NSCLC. N Eng J Med 2020 Oct 1; 383:1328-1339.Atezolizumab for First-Line Treatment of PD-L1–Selected Patients with NSCLC | NEJM
- Spigel D et al. IMpower110: interim overall survival (OS) analysis of a phase III study of atezolizumab (atezo) vs platinum-based chemotherapy (chemo) as first-line (1L) treatment (tx) in PD-L1-selected NSCLC. Ann Oncol. 2019; 30(Suppl 5):v915.IMpower110: Interim overall survival (OS) analysis of a phase III study of atezolizumab (atezo) vs platinum-based chemotherapy (chemo) as first-line (1L) treatment (tx) in PD-L1–selected NSCLC - Annals of Oncology
- Sezer A et al. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet. 2021; 397:592-604.Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial - The Lancet
- Gogishvili M et al. Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 tiral. Nature 2022; 28:2374-80.Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial | Nature Medicine
- Johnson M et al. Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: The Phase III POSEIDON Study. JCO 2022; 41:1213-27.Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non–Small-Cell Lung Cancer: The Phase III POSEIDON Study | Journal of Clinical Oncology (ascopubs.org)
Metastatic: First line, squamous or nonsquamous, PD-L1 TPS<50%, no driver mutation
- Gandhi L et al. Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer. N Eng J Med 2018; 378:2078-92.Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer | NEJM
- Gadgeel S, Rodriguez-Abreu D, Speranza G, et al. Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non–Small-Cell Lung Cancer. J Clin Oncol. 2020; 38:1505-17.Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non–Small-Cell Lung Cancer | Journal of Clinical Oncology (ascopubs.org)
- Paz-Ares L, Luft A, Vicente D et al. Pembrolizumab plus Chemotherapy for Squamous Non–Small-Cell Lung Cancer. N Eng J Med. 2018; 379:2040-51.Pembrolizumab plus Chemotherapy for Squamous Non–Small-Cell Lung Cancer | NEJM
- Socinski M et al. Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. N Eng J Med 2018; 378:2288-2301.Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC | NEJM
- West H et al. Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019; 20:924-37.Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): a multicentre, randomised, open-label, phase 3 trial - The Lancet Oncology
- Hellmann MD et al. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer. N Eng J Med 2019; 381:2020-31.Nivolumab plus Ipilimumab in Advanced Non–Small-Cell Lung Cancer | NEJM
- Paz-Ares L et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2021; 22:198-211.First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial - The Lancet Oncology
- Jotte R et al. Atezolizumab in Combination with Carboplatin and Nab-Paclitaxel in Advanced Squamous NSCLC (IMpower131): Results From a Randomized Phase III Trial. J Thorac Oncol. 2020 Aug; 15:1351-1360.Atezolizumab in Combination With Carboplatin and Nab-Paclitaxel in Advanced Squamous NSCLC (IMpower131): Results From a Randomized Phase III Trial - Journal of Thoracic Oncology (jto.org)
- Gogishvili M et al. Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 tiral. Nature 2022; 28:2374-80.Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial | Nature Medicine
- Johnson M et al. Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: The Phase III POSEIDON Study. JCO 2022; 41:1213-27.Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non–Small-Cell Lung Cancer: The Phase III POSEIDON Study | Journal of Clinical Oncology (ascopubs.org)
Metastatic: Subsequent Therapy, squamous or nonsquamous, no actionable mutation
- Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016; 387:1540-50.Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial - The Lancet
- Herbst RS et al. Long-term outcomes and retreatment among patients with previously treated, programmed death-ligand 1-positive, advanced non-small-cell lung cancer in the KEYNOTE-010 study. J Clin Oncol. 2020; 38:1580-90.Long-Term Outcomes and Retreatment Among Patients With Previously Treated, Programmed Death-Ligand 1‒Positive, Advanced Non‒Small-Cell Lung Cancer in the KEYNOTE-010 Study | Journal of Clinical Oncology (ascopubs.org)
- Herbst RS et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016; 387:1540-50.Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial - The Lancet
- Borghaei H et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Eng J Med 2015; 373:1627-39.Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer | NEJM
- Vokes EE et al. Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases. Ann Oncol. 2018; 29:959-65.Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases - Annals of Oncology
- Brahmer J, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Eng J Med 2015; 373:123-35.Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer | NEJM
- Rittmeyer A et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017; 389:255-65.Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial - The Lancet
- Hanna N et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004; 22:1589-97.Randomized Phase III Trial of Pemetrexed Versus Docetaxel in Patients With Non–Small-Cell Lung Cancer Previously Treated With Chemotherapy | Journal of Clinical Oncology (ascopubs.org)
- Fossella FV et al. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group. J Clin Oncol. 2000 Jun; 18:2354-62.Randomized Phase III Trial of Docetaxel Versus Vinorelbine or Ifosfamide in Patients With Advanced Non–Small-Cell Lung Cancer Previously Treated With Platinum-Containing Chemotherapy Regimens | Journal of Clinical Oncology (ascopubs.org)
- Anderson H et al. Gemcitabine plus best supportive care (BSC) vs BSC in inoperable non-small cell lung cancer--a randomized trial with quality of life as the primary outcome. UK NSCLC Gemcitabine Group. Non-Small Cell Lung Cancer. British Journal of Cancer. 2000; 83:447-53.Gemcitabine plus best supportive care (BSC) vs BSC in inoperable non-small cell lung cancer – a randomized trial with quality of life as the primary outcome | British Journal of Cancer (nature.com)
- Garon EB et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, doubleblind, randomised phase 3 trial. Lancet. 2014; 384:665-73.Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial - The Lancet
- Morgensztern D et al. ABOUND.2L+:A randomized phase 2 study of nanoparticle albumin-bound paclitaxel with or without CC-486 as second-line treatment for advanced nonsquamous non-small cell lun cancer (NSCLC). Cancer 2018; 124:4667-75.ABOUND.2L+: A randomized phase 2 study of nanoparticle albumin‐bound paclitaxel with or without CC‐486 as second‐line treatment for advanced nonsquamous non‐small cell lung cancer (NSCLC) - Morgensztern - 2018 - Cancer - Wiley Online Library
Metastatic: First line, EGFR exon 19 deletion or exon 21 L858R mutations
- Soria JC et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med 2018; 378: 113-125 Osimertinib in Untreated EGFR-Mutated Advanced Non–Small-Cell Lung Cancer | New England Journal of Medicine
- Ramalingam SS et al. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med 2020;382:41-50. Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC | New England Journal of Medicine
- Planchard D et al. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Eng J Med 2023;389:1935-48. Osimertinib with or without Chemotherapy in EGFR-Mutated Advanced NSCLC | New England Journal of Medicine
- Cho BC et al. Amivantamab plus Lazertinib in previously untreated EGFR-mutated advanced NSCLC. N Eng J Med 2024;391:1486-98. Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC | New England Journal of Medicine
Lung Cancer: Small Cell Lung Cancer Pathways:
| Limited Stage Disease
|
Extensive Stage Disease: First Line
|
Extensive Stage Disease: Subsequent Therapy
|
References
Limited Stage Disease
- Turrisi AT et al. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. 1999; 340:265-71.Twice-Daily Compared with Once-Daily Thoracic Radiotherapy in Limited Small-Cell Lung Cancer Treated Concurrently with Cisplatin and Etoposide | NEJM
- Faivre-Finn C et al. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial. Lancet Oncol. 2017; 18:1116-25.Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial - The Lancet Oncology
- Okamoto H et al. Phase II study of area under the plasma-concentration-versus-time curve-based carboplatin plus standarddose intravenous etoposide in elderly patients with small-cell lung cancer. J Clin Oncol. 1999; 17:3540-5Phase II Study of Area Under the Plasma-Concentration-Versus-Time Curve–Based Carboplatin Plus Standard-Dose Intravenous Etoposide in Elderly Patients With Small-Cell Lung Cancer | Journal of Clinical Oncology (ascopubs.org)
- Skarlos DV et al. Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG). Ann Oncol. 2001; 12: 1231-8.Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: A randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG) - Annals of Oncology
Extensive Stage Disease: First Line
- Hanna N et al. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. 2006; 24:2038-43.Randomized Phase III Trial Comparing Irinotecan/Cisplatin With Etoposide/Cisplatin in Patients With Previously Untreated Extensive-Stage Disease Small-Cell Lung Cancer | Journal of Clinical Oncology (ascopubs.org)
- Noda K et al. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med. 2002; 346:85-91.Irinotecan plus Cisplatin Compared with Etoposide plus Cisplatin for Extensive Small-Cell Lung Cancer | NEJM
- Niell HB et al. Randomized phase III intergroup trial of etoposide and cisplatin with or without paclitaxel and granulocyte colony-stimulating factor in patients with extensive-stage small-cell lung cancer: Cancer and Leukemia Group B Trial 9732. J Clin Oncol. 2005; 23:3752-9.Randomized Phase III Intergroup Trial of Etoposide and Cisplatin With or Without Paclitaxel and Granulocyte Colony-Stimulating Factor in Patients With Extensive-Stage Small-Cell Lung Cancer: Cancer and Leukemia Group B Trial 9732 | Journal of Clinical Oncology (ascopubs.org)
- Paz-Ares L et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019; 394:1929-39.Durvalumab plus platinum–etoposide versus platinum–etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial - The Lancet
- Horn L et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018; 379:2220-9.First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer | NEJM
- Schmittel A et al. A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer. Ann Oncol. 2006; 17:663-7.A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer (annalsofoncology.org)
- Schmittel A et al. A German multicenter, randomized phase III trial comparing irinotecan–carboplatin with etoposide–carboplatin as first-line therapy for extensive-disease small-cell lung cancer. Ann Oncol. 2011; 22:1798-1804.A German multicenter, randomized phase III trial comparing irinotecan–carboplatin with etoposide–carboplatin as first-line therapy for extensive-disease small-cell lung cancer - Annals of Oncology
Extensive Stage Disease: Subsequent Therapy
- Von Pawel J et al. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol. 1999; 17:658-67.Topotecan Versus Cyclophosphamide, Doxorubicin, and Vincristine for the Treatment of Recurrent Small-Cell Lung Cancer | Journal of Clinical Oncology (ascopubs.org)
- O'Brien ME et al. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol. 2006; 24:5441-7.Phase III Trial Comparing Supportive Care Alone With Supportive Care With Oral Topotecan in Patients With Relapsed Small-Cell Lung Cancer | Journal of Clinical Oncology (ascopubs.org)
- Eckardt JR et al. Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol. 2007; 25:2086-92.Phase III Study of Oral Compared With Intravenous Topotecan As Second-Line Therapy in Small-Cell Lung Cancer | Journal of Clinical Oncology (ascopubs.org)
- Trigo J et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020; 21:645-54.Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial - The Lancet Oncology
- Antonia SJ et al. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2016; 17:883-95.Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial - The Lancet Oncology
- Ready NE et al. Nivolumab monotherapy and nivolumab plus ipilimumab in recurrent small cell lung cancer: results from the CheckMate 032 randomized cohort. J Thorac Oncol. 2020; 15:426-35.Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Recurrent Small Cell Lung Cancer: Results From the CheckMate 032 Randomized Cohort - Journal of Thoracic Oncology (jto.org)
- Owonikoko T.K. et al. Nivolumab (nivo) plus ipilimumab (ipi), nivo, or placebo (pbo) as maintenance therapy in patients (pts) with extensive disease small cell lung cancer (ED-SCLC) after first-line (1L) platinum-based chemotherapy (chemo): Results from the double-blind, randomized phase III CheckMate 451 study. 2019; 30:1177.Nivolumab (nivo) plus ipilimumab (ipi), nivo, or placebo (pbo) as maintenance therapy in patients (pts) with extensive disease small cell lung cancer (ED-SCLC) after first-line (1L) platinum-based chemotherapy (chemo): Results from the double-blind, randomized phase III CheckMate 451 study - Annals of Oncology
- Rudin CM et al. Pembrolizumab or placebo plus etoposide and platinum as first-line therapy for extensive-stage small-cell lung cancer: randomized, double-blind, phase III KEYNOTE-604 study. J Clin Oncol. 2020; 38:2369-79.Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study | Journal of Clinical Oncology (ascopubs.org)
Melanoma Pathways:
| Stage III, Clinical Node Positive, Resectable Disease, Neoadjuvant/Adjuvant
|
Metastatic: First Line, BRAF Mutation Positive
|
Metastatic: First Line, BRAF Mutation Negative
|
References
Stage III, clinical node positive, resectable disease, neoadjuvant/adjuvant
- Blank CU et al. Neoadjuvant nivolumab and ipilimumab in resectable stage III melanoma. N Eng J Med 2024;391:1696-1708Neoadjuvant Nivolumab and Ipilimumab in Resectable Stage III Melanoma | New England Journal of Medicine
- Patel SP et al. Neoadjuvant-adjuvant or adjuvant-only pembrolizumab in advanced melanoma. N Engl J Med 2023;388:813-23Neoadjuvant–Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma | New England Journal of Medicine
- Amaria RN et al. Neoadjuvant relatlimab and nivolumab in resectable melanoma. Nature 2022;611:155-160. Erratum in: Nature 2023;615:E23Neoadjuvant relatlimab and nivolumab in resectable melanoma - PMC
- Amaria RN et al. Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma. Nat Med 2018;24:1649-54. Erratum in: Nat Med. 2018;24:1941-42.Neoadjuvant Immune Checkpoint Blockade in High-Risk Resectable Melanoma - PMC
Metastatic: First line therapy, BRAF mutated
- Larkin J, Ascierto PA, Dreno B, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014; 371(20):1867-76.Combined Vemurafenib and Cobimetinib in BRAF-Mutated Melanoma | NEJM
- Ascierto PA, McArthur GA, Dreno B, et al. Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol. 2016; 17(9):1248-60.Cobimetinib combined with vemurafenib in advanced BRAFV600-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial - The Lancet Oncology
- Long GV, Stroyakovskiy D, Gogas H, et al. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet. 2015; 386(9992):444-51.Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial - The Lancet
- Long GV, Flaherty KT, Stroyakovskiy D, et al. Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/Kmutant melanoma: long-term survival and safety analysis of a phase 3 study. Ann Oncol. 2017; 28:1631-9.Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: long-term survival and safety analysis of a phase 3 study - Annals of Oncology
- Robert C, Karaszewska B, Schachter J, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015; 372(1):30-9.Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib | NEJM
- Dummer R, Ascierto PA, Gogas HJ, et al. Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2018; 19(5):603-15.Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial - The Lancet Oncology
Metastatic: First line therapy, BRAF mutation negative
- Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015; 372(26):2521-32.Pembrolizumab versus Ipilimumab in Advanced Melanoma | NEJM
- Schachter J, Ribas A, Long GV, et al. Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Lancet. 2017; 390(10105):1853-62.Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006) - The Lancet
- Robert C, Ribas A, Schachter J, et al. Pembrolizumab versus ipilimumab in advanced melanoma (KEYNOTE-006): post-hoc 5-year results from an openlabel, multicentre, randomised, controlled, phase 3 study. Lancet Oncol. 2019; 20(9):1239-51.Pembrolizumab versus ipilimumab in advanced melanoma (KEYNOTE-006): post-hoc 5-year results from an open-label, multicentre, randomised, controlled, phase 3 study - The Lancet Oncology
- Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015; 373(1):23-34.Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma | NEJM
- Hodi FS, Chiarion-Sileni V, Gonzalez R, et al. Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial. Lancet Oncol. 2018; 19(11):1480-92.Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial - The Lancet Oncology
- Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2019; 381(16):1535-46.Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma | NEJM
- Tawbi H et al. Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma. N Eng J Med. 2022; 386:24-34.Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma | NEJM
Multiple Myeloma Pathways:
| First Line: Transplant Eligible
|
First Line: Transplant Deferred or Not Indicated
|
References
First line: Transplant eligible
- Roussel M, Lauwers-Cances V, Robillard N, et al. Front-line transplantation program with lenalidomide, bortezomib, and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple myeloma: a phase II study by the Intergroupe Francophone du Myelome. J Clin Oncol. 2014; 32(25):2712-7.Front-Line Transplantation Program With Lenalidomide, Bortezomib, and Dexamethasone Combination As Induction and Consolidation Followed by Lenalidomide Maintenance in Patients With Multiple Myeloma: A Phase II Study by the Intergroupe Francophone du Myélome | Journal of Clinical Oncology (ascopubs.org)
- Voorhees PM, Kaufman JL, Laubach J, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020; 136(8):936-45.Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial | Blood | American Society of Hematology (ashpublications.org)
- Kumar S, Flinn I, Richardson PG, et al. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012; 119(19):4375-82.Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma | Blood | American Society of Hematology (ashpublications.org)
- Sonneveld P et al. Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. NEJM 2024; 390:301-13.Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma | New England Journal of Medicine (nejm.org)
- Mai EK, Bertsch U, Pozek E, et al. Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone Induction Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma: Final Part 1 Analysis of the GMMG-HD7 Trial. J Clin Oncol. 2025;43(11):1279-1288. doi: 10.1200/JCO-24-02266. Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone Induction Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma: Final Part 1 Analysis of the GMMG-HD7 Trial
First line: Transplant deferred or not indicated
- Durie BG, Hoering A, Abidi MH, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017; 389(10068):519-27.Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial - The Lancet
- Facon T, Kumar S, Plesner T, et al. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med. 2019; 380(22):2104- 15.Oral ixazomib, lenalidomide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma | Blood | American Society of Hematology (ashpublications.org)Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma | NEJM
- Kumar SK, Jacobus SJ, Cohen AD, et al. Carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for patients with newly diagnosed multiple myeloma without intention for immediate autologous stem-cell transplantation (ENDURANCE): a multicentre, open-label, phase 3, randomised, controlled trial. Lancet Oncol. 2020; 21(10):1317-30.Carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for patients with newly diagnosed multiple myeloma without intention for immediate autologous stem-cell transplantation (ENDURANCE): a multicentre, open-label, phase 3, randomised, controlled trial - The Lancet Oncology
- Mateos MV, Dimopoulos MA, Cavo M, et al. Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N Engl J Med. 2018; 378(6):518-28.Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma | NEJM
- Mateos MV, Cavo M, Blade J, et al. Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial. Lancet. 2020; 395(10218):132-41. Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial - The Lancet
- Facon T, et al.. Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2024;391(17):1597-1609. Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma
- Usmani SZ, et al. Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: the randomized phase 3 CEPHEUS trial. Nat Med. 2025;31(4):1195-1202. Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: the randomized phase 3 CEPHEUS trial
Myelodysplastic Syndrome (MDS) Pathways:
| IPSS-R: Intermediate, High, Very High, Non-Transplant Candidate
|
References
IPSS-R: intermediate, high, very high, non-transplant candidate
- Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009 Mar; 10(3):223-32.Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study - The Lancet Oncology
- Lübbert M, Suciu S, Baila L, et al. Low-dose decitabine versus best supportive care in elderly patients with intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group. J Clin Oncol. 2011 May 20; 29(15):1987-96. Low-Dose Decitabine Versus Best Supportive Care in Elderly Patients With Intermediate- or High-Risk Myelodysplastic Syndrome (MDS) Ineligible for Intensive Chemotherapy: Final Results of the Randomized Phase III Study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group | Journal of Clinical Oncology (ascopubs.org)
- Garcia-Manero G, Griffiths EA, Steensma DP et al. Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. Blood. 2020 Aug 6; 136(6):674-683.Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study | Blood | American Society of Hematology (ashpublications.org)
- Bataller A, et al. Oral decitabine plus cedazuridine and venetoclax in patients with higher-risk myelodysplastic syndromes or chronic myelomonocytic leukaemia: a single-centre, phase 1/2 study. Lancet Haematol. 2024;11(3):e186-e195. Oral decitabine plus cedazuridine and venetoclax in patients with higher-risk myelodysplastic syndromes or chronic myelomonocytic leukaemia: a single-centre, phase 1/2 study
- Garcia JS, et al. Efficacy and safety of venetoclax plus azacitidine for patients with treatment-naive high-risk myelodysplastic syndromes. Blood. 2025;145(11):1126-1135. Efficacy and safety of venetoclax plus azacitidine for patients with treatment-naive high-risk myelodysplastic syndromes
Neuroendocrine Cancer Pathways:
| Metastatic, Poorly-Differentiated, Large or Small Cell (Extrapulmonary)
|
References
Metastatic, Poorly-differentiated, Large or Small Cell (Extrapulmonary)
- Iwasa S, Morizane C, Okusaka T, et al. Cisplatin and etoposide as first-line chemotherapy for poorly differentiated neuroendocrine carcinoma of the hepatobiliary tract and pancreas. Jpn J Clin Oncol. 2010 Apr; 40(4):313-8.Cisplatin and Etoposide as First-line Chemotherapy for Poorly Differentiated Neuroendocrine Carcinoma of the Hepatobiliary Tract and Pancreas | Japanese Journal of Clinical Oncology | Oxford Academic (oup.com)
- Frizziero M, Spada F, Lamarca A, et al. Carboplatin in Combination with Oral or Intravenous Etoposide for Extra-Pulmonary, Poorly-Differentiated Neuroendocrine Carcinomas. Neuroendocrinology. 2019; 109(2):100-112.Carboplatin in Combination with Oral or Intravenous Etoposide for Extra-Pulmonary, Poorly-Differentiated Neuroendocrine Carcinomas - Abstract - Neuroendocrinology 2019, Vol. 109, No. 2 - Karger Publishers
- Hanna N et al. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. 2006; 24:2038-43.Randomized Phase III Trial Comparing Irinotecan/Cisplatin With Etoposide/Cisplatin in Patients With Previously Untreated Extensive-Stage Disease Small-Cell Lung Cancer | Journal of Clinical Oncology (ascopubs.org)
- Schmittel A et al. A German multicenter, randomized phase III trial comparing irinotecan–carboplatin with etoposide–carboplatin as first-line therapy for extensive-disease small-cell lung cancer. Ann Oncol. 2011; 22:1798-1804.A German multicenter, randomized phase III trial comparing irinotecan–carboplatin with etoposide–carboplatin as first-line therapy for extensive-disease small-cell lung cancer - Annals of Oncology
- Hadoux J, Malka D, Planchard D, et al. Post-first-line FOLFOX chemotherapy for grade 3 neuroendocrine carcinoma. Endocr Relat Cancer. 2015 Jun; 22(3):289-98.Post-first-line FOLFOX chemotherapy for grade 3 neuroendocrine carcinoma in: Endocrine-Related Cancer Volume 22 Issue 3 (2015) (bioscientifica.com)
- Hentic O, Hammel P, Couvelard A, et al. FOLFIRI regimen: an effective second-line chemotherapy after failure of etoposide-platinum combination in patients with neuroendocrine carcinomas grade 3. Endocr Relat Cancer. 2012 Nov 6; 19(6):751-7.FOLFIRI regimen: an effective second-line chemotherapy after failure of etoposide–platinum combination in patients with neuroendocrine carcinomas grade 3 in: Endocrine-Related Cancer Volume 19 Issue 6 (2012) (bioscientifica.com)
- Zhu J, Strosberg JR, Dropkin E, et al. Treatment of High-Grade Metastatic Pancreatic Neuroendocrine Carcinoma with FOLFIRINOX. J Gastrointest Cancer. 2015 Jun; 46(2):166-9.Treatment of High-Grade Metastatic Pancreatic Neuroendocrine Carcinoma with FOLFIRINOX | SpringerLink
- Rogowski W, Wachula E, Gorzelak A, et al. Capecitabine and temozolomide combination for treatment of high-grade, well-differentiated neuroendocrine tumour and poorly-differentiated neuroendocrine carcinoma - retrospective analysis. Endokrynol Pol. 2019; 70(4):313-317.Capecitabine and temozolomide combination for treatment of high-grade, well-differentiated neuroendocrine tumour and poorly-differentiated neuroendocrine carcinoma — retrospective analysis | Rogowski | Endokrynologia Polska (viamedica.pl)
- Klein O, Kee D, Markman B, et al. Immunotherapy of Ipilimumab and Nivolumab in Patients with Advanced Neuroendocrine Tumors: A Subgroup Analysis of the CA209-538 Clinical Trial for Rare Cancers. Clin Cancer Res. 2020 Sep 1; 26(17):4454-4459. Immunotherapy of Ipilimumab and Nivolumab in Patients with Advanced Neuroendocrine Tumors: A Subgroup Analysis of the CA209-538 Clinical Trial for Rare Cancers | Clinical Cancer Research | American Association for Cancer Research (aacrjournals.org)
- Marabelle A, Fakih M, Lopez J, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol. 2020 Oct; 21(10):1353-1365.Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study - The Lancet Oncology
Ovarian Cancer Pathways:
| Primary Therapy: Stage II-IV
|
Recurrent Disease, Platinum Sensitive
|
References
Primary therapy: Stage II-IV
- du Bois A, Luck HJ, Meier W, et al. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst 2003; 95:1320 –30.Randomized Clinical Trial of Cisplatin/Paclitaxel Versus Carboplatin/Paclitaxel as First-Line Treatment of Ovarian Cancer | JNCI: Journal of the National Cancer Institute | Oxford Academic (oup.com)
- Bookman MA, Brady MF, McGuire WP, et al. Evaluation of new platinum-based treatment regimens in advanced-stage ovarian cancer: a phase III Trial of the Gynecologic Cancer Intergroup. J Clin Oncol. 2009; 27(9):1419-25.Evaluation of New Platinum-Based Treatment Regimens in Advanced-Stage Ovarian Cancer: A Phase III Trial of the Gynecologic Cancer InterGroup | Journal of Clinical Oncology (ascopubs.org)
- Perren T, Swart AM, Pfisterer J, et al. A Phase 3 Trial of Bevacizumab in Ovarian Cancer. N Eng J Med. 2011; 365:2484-96. A Phase 3 Trial of Bevacizumab in Ovarian Cancer | NEJM
- Oza AM, Cook AD, Pfisterer J, et al. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol. 2015 Aug; 16(8):928-36. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial - The Lancet Oncology
- Burger RA, Brady MF, Bookman MA, et al. Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer. N Eng J Med. 2011; 365:2473-83.Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer (nejm.org)
- Tewari KS, Burger RA, Enserro D, et al. Final Overall Survival of a Randomized Trial of Bevacizumab for Primary Treatment of Ovarian Cancer. J Clin Oncol. 2019 Sep 10; 37(26):2317-28. Final Overall Survival of a Randomized Trial of Bevacizumab for Primary Treatment of Ovarian Cancer | Journal of Clinical Oncology (ascopubs.org)
Recurrent disease, platinum sensitive
- Pfisterer J, Plante M, Vergote I, et al. Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG. J Clin Oncol. 2006; 24(29):4699-707.Gemcitabine Plus Carboplatin Compared With Carboplatin in Patients With Platinum-Sensitive Recurrent Ovarian Cancer: An Intergroup Trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG | Journal of Clinical Oncology (ascopubs.org)
- Aghajanian C, Blank SV, Goff BA, et al. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012; 30(17):2039-45.OCEANS: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Chemotherapy With or Without Bevacizumab in Patients With Platinum-Sensitive Recurrent Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer | Journal of Clinical Oncology (ascopubs.org)
- Aghajanian C, Goff B, Nycum LR, et al. Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer. Gynecol Oncol. 2015; 139(1):10-6.Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer - Gynecologic Oncology (gynecologiconcology-online.net)
- Wagner U, Marth C, Largillier R, et al. Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients. British Journal of Cancer. 2012; 107(4):588-91.Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients | British Journal of Cancer (nature.com)
- Coleman RL, Brady MF, Herzog TJ, et al. Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Jun; 18(6):779-791.Bevacizumab and paclitaxel–carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial - The Lancet Oncology
- Pfisterer J, Shannon CM, Baumann K, et al. Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. Lancet Oncol. 2020; 21(5):699-709.Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial - The Lancet Oncology
Pancreatic Cancer Pathways:
| Adenocarcinoma: Neoadjuvant Therapy
|
||
| Adenocarcinoma, Advanced/Metastatic: First Line Therapy
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References
Adenocarcinoma: Neoadjuvant
- Katz MH, Shi Q, Ahmad SA, Herman JM, et al. Preoperative Modified FOLFIRINOX Treatment Followed by Capecitabine-Based Chemoradiation for Borderline Resectable Pancreatic Cancer: Alliance for Clinical Trials in Oncology Trial A021101. JAMA Surg. 2016 Aug 17; 151(8):e161137.Preoperative Modified FOLFIRINOX Treatment Followed by Capecitabine-Based Chemoradiation for Borderline Resectable Pancreatic Cancer: Alliance for Clinical Trials in Oncology Trial A021101 | Endocrine Surgery | JAMA Surgery | JAMA Network
- Murphy JE, Wo JY, Ryan DP, et al. Total Neoadjuvant Therapy With FOLFIRINOX Followed by Individualized Chemoradiotherapy for Borderline Resectable Pancreatic Adenocarcinoma: A Phase 2 Clinical Trial. JAMA Oncol.2018; 4(7):963–969.Total Neoadjuvant Therapy With FOLFIRINOX Followed by Individualized Chemoradiotherapy for Borderline Resectable Pancreatic Adenocarcinoma: A Phase 2 Clinical Trial | Gastroenterology | JAMA Oncology | JAMA Network
- O'Reilly EM, Lee JW, Zalupski M, et al. Randomized, multicenter, phase II trial of gemcitabine and cisplatin with or without veliparib in patients with pancreas adenocarcinoma and a germline BRCA/PALB2 mutation. J Clin Oncol 2020; 38:1378-88.Randomized, Multicenter, Phase II Trial of Gemcitabine and Cisplatin With or Without Veliparib in Patients With Pancreas Adenocarcinoma and a Germline BRCA/PALB2 Mutation | Journal of Clinical Oncology (ascopubs.org)
- Sohal DPS, Duong M, Ahmad SA, et al. Efficacy of Perioperative Chemotherapy for Resectable Pancreatic Adenocarcinoma: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2021; 7(3):421–427.Efficacy of Perioperative Chemotherapy for Resectable Pancreatic Adenocarcinoma: A Phase 2 Randomized Clinical Trial | Clinical Pharmacy and Pharmacology | JAMA Oncology | JAMA Network
Adenocarcinoma, Advanced/Metastatic: First line
- Conroy T et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. NEJM 2011; 364:1817-25.FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer | New England Journal of Medicine (nejm.org)
- Von Hoff DD et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. NEJM 2013; 369:1691-1703.Increased Survival in Pancreatic Cancer with nab-Paclitaxel plus Gemcitabine | New England Journal of Medicine (nejm.org)
- Wainberg Z et al. NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naïve patients with metastatic pancreatic ductal adecnocarcinoma (NAPOLI 3): a randomized, open-label, phase 3 trial. Lancet 2023; 402:1272-81.NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial - The Lancet
Prostate Cancer Pathways:
| Metastatic: Adenocarcinoma, Castration Resistant
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References
Metastatic: Adenocarcinoma, Castration Resistant
- Ryan C et al. Abiraterone in Metastatic Prostate Cancer without Previous Chemotherapy. NEJM 2013; 368:138-48.Abiraterone in Metastatic Prostate Cancer without Previous Chemotherapy | New England Journal of Medicine (nejm.org))
- Beer T et al. Enzalutamide in Metastatic Prostate Cancer before Chemotherapy. NEJM 2014; 371:424-33.Enzalutamide in Metastatic Prostate Cancer before Chemotherapy | New England Journal of Medicine (nejm.org)
- Tannock I et al. Docetaxel plus Prednisone or Mitoxantrone plus Prednisone for Advanced Prostate Cancer. NEJM 2004; 351:1502-12.Docetaxel plus Prednisone or Mitoxantrone plus Prednisone for Advanced Prostate Cancer | New England Journal of Medicine (nejm.org)
- Sebastian de Bono J et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomized open-label trial. Lancet 2010; 376:1147-54.Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial - The Lancet
- Kantoff P et al. Sipuleucel-T Immunotherapy for Castration-Resistant Prostate Cancer. NEJM 2010; 363:411-22.Sipuleucel-T Immunotherapy for Castration-Resistant Prostate Cancer | New England Journal of Medicine (nejm.org)
Testicular Cancer Pathways:
| First Line: Good Risk
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First Line: Intermediate/Poor Risk
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References
First Line: Good Risk
- Saxman SB, Finch D, Gonin R, et al. Long-term follow-up of a phase III study of three versus four cycles of bleomycin, etoposide, and cisplatin in favorable-prognosis germ-cell tumors: the Indian University experience. J Clin Oncol. 1998;16(2):702-6.Long-term follow-up of a phase III study of three versus four cycles of bleomycin, etoposide, and cisplatin in favorable-prognosis germ-cell tumors: the Indian University experience. | Journal of Clinical Oncology (ascopubs.org)
- Culine S, Kerbrat P, Kramar A, et al. Refining the optimal chemotherapy regimen for good-risk metastatic nonseminomatous germ-cell tumors: a randomized trial of the Genito-Urinary Group of the French Federation of Cancer Centers (GETUG T93BP). Ann Oncol. 2007 May; 18(5):917-24. Refining the optimal chemotherapy regimen for good-risk metastatic nonseminomatous germ-cell tumors: a randomized trial of the Genito-Urinary Group of the French Federation of Cancer Centers (GETUG T93BP) - Annals of Oncology
First Line: Intermediate/Poor Risk
- de Wit R, Stoter G, Sleijfer DT, et al. Four cycles of BEP vs four cycles of VIP in patients with intermediate-prognosis metastatic testicular non-seminoma: a randomized study of the EORTC Genitourinary Tract Cancer Cooperative Group. European Organization for Research and Treatment of Cancer. Br J Cancer. 1998 Sep; 78(6):828-32. Four cycles of BEP vs four cycles of VIP in patients with intermediate-prognosis metastatic testicular non-seminoma: a randomized study of the EORTC Genitourinary Tract Cancer Cooperative Group | British Journal of Cancer (nature.com)
- Culine S, Kramar A, Théodore C, et al. Randomized trial comparing bleomycin/etoposide/cisplatin with alternating cisplatin/cyclophosphamide/doxorubicin and vinblastine/bleomycin regimens of chemotherapy for patients with intermediate- and poor-risk metastatic nonseminomatous germ cell tumors: Genito-Urinary Group of the French Federation of Cancer Centers Trial T93MP. J Clin Oncol. 2008 Jan 20; 26(3):421-7.Randomized Trial Comparing Bleomycin/Etoposide/Cisplatin With Alternating Cisplatin/Cyclophosphamide/Doxorubicin and Vinblastine/Bleomycin Regimens of Chemotherapy for Patients With Intermediate- and Poor-Risk Metastatic Nonseminomatous Germ Cell Tumors: Genito-Urinary Group of the French Federation of Cancer Centers Trial T93MP | Journal of Clinical Oncology (ascopubs.org)
- Nichols CR, Catalano PJ, Crawford ED, et al. Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study. J Clin Oncol. 1998 Apr; 16(4):1287-93.Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study. | Journal of Clinical Oncology (ascopubs.org)