Indirect treatment comparison of nivolumab versus placebo as adjuvant treatment for resected melanoma

Abstract

Background: Nivolumab (an anti-programmed death-1 antibody) is an adjuvant standard of care for patients with high-risk resected melanoma, although a watch-and-wait strategy remains an option. In the absence of head-to-head evidence, an indirect treatment comparison (ITC) of adjuvant nivolumab versus placebo, the proxy for a watch-and-wait strategy, was conducted in patients with high-risk resected melanoma.

Methods: An ITC using the Bucher method compared nivolumab with placebo using intention-to-treat population data from the phase III CheckMate 238 (nivolumab vs ipilimumab; minimum follow-up, 4 years; NCT02388906) and European Organisation for Research and Treatment of Cancer (EORTC) 18071 (ipilimumab vs placebo; minimum follow-up, ≈4.5 years; NCT00636168) trials. The end-points were recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and overall survival (OS). To account for cross-trial differences in staging and subsequent therapy, additional analyses examined patients with stage IIIB/IIIC disease and adjusted post-recurrence survival in EORTC 18071, respectively.

Results: Nivolumab versus placebo was associated with clinically meaningful improvements in RFS (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.42-0.68) and OS (HR, 0.63; 95% CI, 0.45-0.89). Nivolumab versus placebo was also associated with clinically meaningful improvements in RFS (HR, 0.53; 95% CI, 0.40-0.69), DMFS (HR, 0.62; 95% CI, 0.46-0.83) and OS (HR, 0.67; 95% CI, 0.47-0.97) in patients with stage IIIB/IIIC disease and in OS (HR, 0.65; 95% CI, 0.46-0.92) in the overall population after adjusting post-recurrence survival in EORTC 18071.

Conclusion: This ITC shows that adjuvant nivolumab provides clinically meaningful improvements in RFS, DMFS and OS versus a watch-and-wait strategy in high-risk resected melanoma.

Keywords: Adjuvant treatment; Anti–programmed death-1 antibody; Distant metastasis-free survival; Indirect treatment comparison; Melanoma; Nivolumab; Overall survival; Recurrence-free survival; Watch-and-wait strategy.

Conflict of interest statement

Conflict of interest statement Jeffrey S. Weber Stock and Other Ownership Interests: Biond, CytoMx, Evaxion, NexImmune, Protean Consulting or Advisory Role: AstraZeneca, Biond, Bristol Myers Squibb (BMS), Celldex, CytomX, Evaxion, GlaxoSmithKline (GSK), Genentech, Idera, Incyte, Merck, NexImmune, Novartis, OncoSec, Pfizer, Ultimovacs, Regeneron, Sellas Research Funding: BMS, GSK, Merck, Moderna, Novartis, Regeneron Patents, Royalties, Other Intellectual Property: Patents issued for a PD-1 biomarker named by Biodesix and a CTLA-4 biomarker named by Moffitt Cancer Center Paolo A. Ascierto Consulting or Advisory Role: 4SC, AstraZeneca, BMS, Boehringer-Ingelheim, Daiichi Sankyo, Eisai, Idera, Immunocore, Italfarmaco, iTeos Lunaphore, Merck Serono, Merck Sharp & Dohme (MSD), Nektar, Nouscom, Novartis, Oncosec, Pfizer, Pierre Fabre, Regeneron, Roche/Genentech, Sandoz, Sanofi, Seagen, Sun Pharma Research Funding: BMS, Pfizer, Roche/Genentech, and Sanofi Mark R. Middleton Consulting or Advisory Role: Array Biopharma, BiolineRx, BMS, Immunocore, Kineta, Merck/MSD, Novartis, Rigontec, Silicon Therapeutics Research Funding: Array BioPharma, AstraZeneca, BiolineRx, BMS, Eisai, GSK, Immunocore, Millennium, Merck/MSD, Novartis, Pfizer, Regeneron, Replimune, Rigontec (acquired by MSD), Roche Travel, Accommodations, Expenses: Merck/MSD, Replimune Delphine Hennicken Employment: BMS Stock and Other Ownership Interests: BMS Roberto Zoffoli Employment: BMS Stock and Other Ownership Interests: BMS Anne Pieters Employment: BMS Stock and Other Ownership Interests: BMS Adenike Amadi Employment: BMS Stock and Other Ownership Interests: BMS Katrin Kupas Employment: BMS Stock and Other Ownership Interests: BMS Srividya Kotapati Employment: BMS Stock and Other Ownership Interests: BMS Andriy Moshyk Employment: BMS Stock and Other Ownership Interests: BMS Dirk Schadendorf Honoraria: 4SC, Amgen, Array BioPharma, BMS, Incyte, Immunocore, InFlarX, Neracare, Novartis, Merck/MSD, Merck Serono, Philogen, Pierre Fabre, Regeneron, Roche/Genentech, Sandoz/Hexal Consulting or Advisory Role: 4SC, Amgen, BMS, Incyte, Immunocore, Merck/MSD, Merck Serono, Mologen, Novartis, Pierre Fabre, Roche/Genentech, Sanofi/Regeneron Speakers' Bureau: Amgen, BMS, Incyte, Novartis, Pierre Fabre Research Funding: 4SC, Amgen, BMS, Merck Serono, Merck/MSD, Novartis, Pierre Fabre, Philogen, Regeneron, Sanofi/Regeneron Travel, Accommodations, Expenses: Amgen, BMS, Merck/MSD, Merck Serono, Novartis, Roche/Genentech No other potential conflicts of interest were reported.

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.