A matching-adjusted indirect comparison of combination nivolumab plus ipilimumab with BRAF plus MEK inhibitors for the treatment of BRAF-mutant advanced melanoma

BACKGROUND

Approved first-line treatments for patients with BRAF V600-mutant advanced melanoma include nivolumab (a programmed cell death protein 1 inhibitor) plus ipilimumab (a cytotoxic T lymphocyte antigen-4 inhibitor; NIVO+IPI) and the BRAF/MEK inhibitors dabrafenib plus trametinib (DAB+TRAM), encorafenib plus binimetinib (ENCO+BINI), and vemurafenib plus cobimetinib (VEM+COBI). Results from prospective randomized clinical trials (RCTs) comparing these treatments have not yet been reported. This analysis evaluated the relative efficacy and safety of NIVO+IPI versus DAB+TRAM, ENCO+BINI, and VEM+COBI in patients with BRAF-mutant advanced melanoma using a matching-adjusted indirect comparison (MAIC).

PATIENTS AND METHODS

A systematic literature review identified RCTs for DAB+TRAM, ENCO+BINI, and VEM+COBI in patients with BRAF-mutant advanced melanoma. Individual patient-level data for NIVO+IPI were derived from the phase III CheckMate 067 trial (BRAF-mutant cohort) and restricted to match the inclusion/exclusion criteria of the comparator trials. Treatment effects for overall survival (OS) and progression-free survival (PFS) were estimated using Cox proportional hazards and time-varying hazard ratio (HR) models. Safety outcomes (grade 3 or 4 treatment-related adverse events) with NIVO+IPI and the comparators were compared.

RESULTS

In the Cox proportional hazards analysis, NIVO+IPI showed improved OS compared with DAB+TRAM (HR = 0.53; 95% confidence interval [CI], 0.39-0.73), ENCO+BINI (HR = 0.60; CI, 0.42-0.85), and VEM+COBI (HR = 0.50; CI, 0.36-0.70) for the overall study period. In the time-varying analysis, NIVO+IPI was associated with significant improvements in OS and PFS compared with the BRAF/MEK inhibitors 12 months after treatment initiation. There were no significant differences between NIVO+IPI and BRAF/MEK inhibitor treatment from 0 to 12 months. Safety outcomes favored DAB+TRAM over NIVO+IPI, whereas NIVO+IPI was comparable to VEM+COBI.

CONCLUSION

Results of this MAIC demonstrated durable OS and PFS benefits for patients with BRAF-mutant advanced melanoma treated with NIVO+IPI compared with BRAF/MEK inhibitors, with the greatest benefits noted after 12 months.

Informations de copyright

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

Déclaration de conflit d'intérêts

Disclosure AAT has served as an advisor/consultant to Array BioPharma, BioNtech, Clinigen, Bristol Myers Squibb, EMD Serono, Genentech/Roche, ImmunoCore, Merck, NewLink Genetics, Novartis, Partner Therapeutics, Pfizer, and Sanofi-Genzyme/Regeneron; and has received institutional research support from Bristol Myers Squibb, Genentech/Roche, Merck, and OncoSec. KT is an employee of Precision HEOR, which was contracted by Bristol Myers Squibb for the current work. KC is an employee of Precision HEOR, which was contracted by Bristol Myers Squibb for the current work. DFM has served as a consultant to Alkermes, Bristol Myers Squibb, Eisai, Eli Lilly, EMD Serono, Iovance, Merck, and Pfizer; and has received research support from Alkermes, Bristol Myers Squibb, Exelixis, Genentech, Merck, Pfizer, and X4 Pharmaceuticals. PM has served as an advisor to Amgen, Bristol Myers Squibb, GSK, Merck KGaA, MSD, Novartis, Pierre Fabre, Roche, and Sanofi; has worked as a speaker for Amgen, Bristol Myers Squibb, GSK, Merck KGaA, MSD, Novartis, Pierre Fabre, Roche, and Sanofi; and has received institutional research support from Bristol Myers Squibb and MSD. JL has served as a consultant to Achilles Therapeutics, AstraZeneca, Aveo, Boston Biomedical, Bristol Myers Squibb, Covance, Eisai, EUSA Pharma, GSK, Immunocore, Imugene, Incyte, iOnctura, Ipsen, Kymab, Merck Serono, MSD, Nektar, Novartis, Pierre Fabre, Pfizer, Pharmacyclics, Roche, Secarna, and Vitaccess; and has received research support from Achilles Therapeutics, Bristol Myers Squibb, Covance, Immunocore, Merck Serono, MSD, Nektar, Novartis, Pierre Fabre, Pfizer, Roche, Secarna, and Vitaccess. FSH has served as an advisor/consultant to Aduro, Apricity, Bristol Myers Squibb, Checkpoint Therapeutics, Compass Therapeutics, Corner Therapeutics, Eisai, EMD Serono, Genentech/Roche, Idera, Kairos, Merck, Novartis, Pionyr, Sanofi, 7 Hills Pharma, Surface, Takeda, Torque, Rheos, Pieris Pharmaceutical, PsiOxus Therapeutics, and Zumutor; holds equity in Bicara and Pionyr; and is named on several patents and patents pending and on patents issued to or pending for Dana-Farber Cancer Institute. CL is an employee of Bristol Myers Squibb. JIR is an employee of Bristol Myers Squibb; holds stocks in Bristol Myers Squibb; and is named on a patent pending for Bristol Myers Squibb. HJ provided consultancy services to Bristol Myers Squibb related to the current work. AM is an employee of Bristol Myers Squibb and holds stock in Bristol Myers Squibb. SR is an employee of Bristol Myers Squibb. SK is an employee of Bristol Myers Squibb. MBA has served as an advisor/consultant to Agenus, Alexion, Apexigen, Arrowhead, Aveo, Bristol Myers Squibb, COTA, Eisai, Exelixis, Genentech/Roche, Idera, ImmunoCore, Iovance, Leads BioPharma, Merck, Neoleukin, Novartis, and PACT, Pfizer, Pneuma, Pyxis Oncology, Third Rock Ventures, and Werewolf; and has received institutional research funding from Bristol Myers Squibb. Data sharing Bristol Myers Squibb's policy on data sharing is available at https://www.bms.com/researchers-and-partners/independent-research/data-sharing-request-process.html.