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. 2019 Dec;8(18):7637-7643.
doi: 10.1002/cam4.2625. Epub 2019 Nov 2.

Real-world survival of patients with advanced BRAF V600 mutated melanoma treated with front-line BRAF/MEK inhibitors, anti-PD-1 antibodies, or nivolumab/ipilimumab

Justin C Moser  1 , Danli Chen  2 , Siwen Hu-Lieskovan  3 , Kenneth F Grossmann  3 , Shiven Patel  3 , Sarah V Colonna  3 , Jian Ying  2 , John R Hyngstrom  4
Affiliations

Real-world survival of patients with advanced BRAF V600 mutated melanoma treated with front-line BRAF/MEK inhibitors, anti-PD-1 antibodies, or nivolumab/ipilimumab

Justin C Moser et al. Cancer Med. 2019 Dec.

Abstract

Background: The optimal treatment sequence for patients with advanced BRAF V600 mutant melanoma is unknown. BRAF/MEK inhibition (BRAF/MEKi), single agent anti-PD-1 (aPD-1) antibodies and combination immune checkpoint inhibition with nivolumab and ipilimumab (niv/ipi) are all approved; however, they have not been prospectively compared. Therefore, we sought to compare overall survival of patients with advanced BRAF mutant melanoma treated with either front-line BRAF/MEKi, aPD-1, or niv/ipi.

Methods: Patients with advanced BRAF mutant melanoma who had received BRAF/MEKi, niv/ipi, or aPD-1 in the front-line setting were identified from a nationwide database comprising de-identified patient-level structured and unstructured data derived from electronic health records. Survival was compared using Kaplan-Meier curves and log-rank analysis. Univariate and multivariate Cox regression models were used to measure the effect of front-line treatment, age (>64 or not), LDH (elevated or not), and Eastern Cooperative Oncology Group (ECOG) performance status (>1 or not) on survival.

Results: Five hundred and sixty seven patients with advanced disease and treated with front-line aPD-1 (n = 162), BRAF/MEKi (n = 297) or niv/ipi (n = 108) were identified. With a median follow-up of 22.4 months, median overall survival (OS) for patients treated with front-line niv/ipi was not reached (NR) while median OS for patients treated with aPD-1 or BRAF/MEKi was 39.5 months and 13.2 months, respectively. Front-line treatment with PD-1 and niv/ipi were associated with statistically longer survival than BRAF/MEKi in multivariate analyses.

Conclusions: In our real-world retrospective analysis, patients with advanced BRAF mutant melanoma treated with front-line niv/ipi or aPD-1 had longer survival compared to those treated with front-line BRAF/MEKi.

Keywords: BRAF; anti-PD-1 antibodies; dabrafenib; melanoma; nivolumab/ipilimumab; pembrolizumab; trametinib.

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Conflict of interest statement

KFG has advised for BMS (within last year), Novartis (2 years ago), Array (within last year), Castle Biosciences (>3 years ago)—all less than 5k annually. SP received institutional research funding from Merck and Takeda. JRH is contracted with Ebix publishers to perform audio reviews of published articles in general surgery; this work is not related to melanoma. SL does consulting for Amgen, Merck, Genmab, Xencor, and BMS; receives research support from BMS, Merck, Vaccinex; and performs contracted research for Pfizer, Plexxikon, Genentech, Neon Therapeutics, Nektar, Astellas, F Star, Xencor.

Figures

Figure 1
Figure 1
Overall survival of patients with advanced BRAF V600 Mutated Melanoma according to front‐line treatment
Figure 2
Figure 2
Time to next‐line therapy or death of patients for advanced BRAF V600 mutated melanomas by front‐line treatment
See this image and copyright information in PMC

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