Reference Detail

Ref Type

Journal Article

PMID

(33556898)

Authors

Tarhini AA, Toor K, Chan K, McDermott DF, Mohr P, Larkin J, Hodi FS, Lee CH, Rizzo JI, Johnson H, Moshyk A, Rao S, Kotapati S, Atkins MB

Title

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

Journal	Vol	Issue	Date	Pages	Journal Short Title
ESMO open	6	2	2021 04	100050	ESMO Open

URL

Abstract Text

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).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.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.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.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
BRAF act mut	melanoma	predicted - sensitive	Ipilimumab + Nivolumab	Clinical Study	Actionable	In a systematic review, an analysis of several clinical trials demonstrated Opdivo (nivolumab) plus Yervoy (ipilimumab) resulted in improved overall survival (OS) compared to BRAF plus MEK inhibitor in BRAF-mutant advanced melanoma patients when considering the entire study period, and analysis of the period beginning 12 months after treatment initiation demonstrated significantly greater OS and progression-free survival (PMID: 33556898; NCT01844505, NCT01584648, NCT01597908, NCT01909453, NCT01689519).	33556898