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

A.A Tarhini,K Toor,K Chan,D.F Mcdermott,P Mohr,J Larkin,F.S Hodi,C.-H Lee,J.I Rizzo,H Johnson,A Moshyk,S Rao,S Kotapati,M.B Atkins

doi:10.1016/j.esmoop.2021.100050

Abstract

BackgroundApproved 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 methodsA 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.ResultsIn 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.ConclusionResults 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.

Highlights

In the time-varying analysis, NIVOþIPI was associated with significant improvements in overall survival (OS) and progression-free survival (PFS) compared with the BRAF/MEK inhibitors 12 months after treatment initiation
Results of this matching-adjusted indirect comparison (MAIC) demonstrated durable OS and PFS benefits for patients with BRAF-mutant advanced melanoma treated with NIVOþIPI compared with BRAF/MEK inhibitors, with the greatest benefits noted after 12 months
Note: This study was previously presented in poster form: Tarhini AA, McDermott DF, Wang R, et al Long-term survival benefit of nivolumab plus ipilimumab versus BRAFþMEK inhibitors for patients with BRAF-mutant advanced melanoma

Summary

Introduction

ESMO Open cutaneous melanoma population.[3] First-line treatments approved by the US Food and Drug Administration (FDA) for patients with BRAF-mutant melanoma includedamong othersdthe immunotherapy combination of nivolumab [a programmed death (PD)-1 inhibitor] plus ipilimumab [a cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor; NIVOþIPI] and targeted therapy combinations with the BRAF/MEK inhibitors dabrafenib plus trametinib Approved first-line treatments for patients with BRAF V600emutant advanced melanoma include nivolumab (a programmed cell death protein 1 inhibitor) plus ipilimumab (a cytotoxic T lymphocyte antigen-4 inhibitor; NIVOþIPI) and the BRAF/MEK inhibitors dabrafenib plus trametinib (DABþTRAM), encorafenib plus binimetinib (ENCOþBINI), and vemurafenib plus cobimetinib (VEMþCOBI). Results from prospective randomized clinical trials (RCTs) comparing these treatments have not yet been reported This analysis evaluated the relative efficacy and safety of NIVOþIPI versus DABþTRAM, ENCOþBINI, and VEMþCOBI in patients with BRAF-mutant advanced melanoma using a matching-adjusted indirect comparison (MAIC)

Methods

Results

Discussion

Conclusion