Background

Approved first-line (1L) treatments for BRAF-mutant (BRAF-MT) advanced melanoma include nivolumab plus ipilimumab (NIVO + IPI), anti–PD-1 monotherapy, and BRAF plus MEK inhibitors (BRAFi + MEKi). Clinical trial data comparing these options are limited. A real-world study in patients (pts) with BRAF-MT melanoma showed 3-year overall survival (OS) of 58% and 27% with NIVO + IPI and BRAFi + MEKi, respectively (Pavlick AC, et al. EADO 2020). The longer-term follow-up is presented here.

Methods

This retrospective, observational study used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database to describe patient characteristics, treatment patterns, and outcomes in pts with BRAF-MT advanced melanoma who initiated 1L therapy between Jan 1, 2011, and Apr 30, 2020 (index date). Study cutoff was Apr 30, 2021, to allow potential follow-up of > 1 year. OS and progression-free survival (PFS) were assessed by Kaplan–Meier estimates and Cox regression analysis. PFS was based on progression status in the database.

Results

This study included pts with BRAF-MT melanoma treated with 1L NIVO + IPI (n = 221), anti–PD-1 monotherapy (n = 343), or BRAFi + MEKi (n = 454). Across the groups, baseline differences were noted for mean age (58.4, 65.1, and 60.4 years, respectively), ECOG performance status ≥ 2 (8%, 18%, and 22% for evaluable pts), and elevated lactate dehydrogenase (30%, 21%, and 37% for evaluable pts). Potential median follow-up from the index date was 35.0, 41.9, and 51.5 months, respectively. Second-line treatment was used in 39%, 42%, and 49% of pts treated with NIVO + IPI, anti–PD-1 monotherapy, and BRAFi + MEKi, respectively. NIVO + IPI and anti–PD-1 monotherapy were associated with longer OS and PFS versus BRAFi + MEKi (Table). Table: 95P

OS and PFS with 1L therapy in BRAF-MT advanced melanoma

Conclusions

In this real-world study of pts with BRAF-MT advanced melanoma, there appeared to be a survival benefit with 1L NIVO + IPI and anti–PD-1 monotherapy relative to 1L BRAFi + MEKi. Ongoing clinical trials may validate these findings.

Editorial acknowledgement

Professional medical writing and editorial assistance were provided by Mark Palangio and Michele Salernitano at Ashfield MedComms, an Ashfield Health company, funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

A. Amin: Financial Interests, Personal, Writing Engagements: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb, Regeneron, Sanofi. A.C. Pavlick: Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Merck, Regeneron, Replimune; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, Regeneron; Financial Interests, Personal, Writing Engagements: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, Regeneron. C. Lee: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Writing Engagements: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb; Financial Interests, Institutional, Funding: Bristol Myers Squibb. E. Chou: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. Y. Zhang: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. L.A. Sakkal: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb; Financial Interests, Personal, Funding: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb. J. Moser: Financial Interests, Personal, Funding: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Amunix, Thirona Bio; Financial Interests, Personal, Speaker’s Bureau: Caris Life Sciences, Daiichi-Sankyo, TGen; Financial Interests, Institutional, Invited Speaker: NovoCure; Financial Interests, Institutional, Invited Speaker: Genentech; Financial Interests, Institutional, Invited Speaker: Alpine Immune Sciences; Financial Interests, Institutional, Funding: Amgen; Financial Interests, Institutional, Funding: Trishula Therapeutics; Financial Interests, Institutional, Funding: BioEclipse Therapeutics, FujiFilm, ImmuneSensor, Simcah, Repertoire Immune Sciences, Nektar Therapuetics, Synthorx Inc, Istari Oncology.