Sequencing Treatment in BRAFV600 Mutant Melanoma: Anti-PD-1 before and after BRAF Inhibition

Douglas B. Johnson*, Eirini Pectasides, Emily Feld, Fei Ye, Shilin Zhao, Romany Johnpulle, Ryan Merritt, David F. McDermott, Igor Puzanov, Donald Lawrence, Jeffrey A. Sosman, Elizabeth Buchbinder, Ryan J. Sullivany

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Novel agents targeting immune checkpoint molecules or mutated BRAF are active therapeutic options for patients with BRAFV600-mutant melanoma. However, the most effective first-line treatment and the optimal sequencing of these agents have not been well characterized. To explore this, we retrospectively assessed 114 patients from 4 centers with advanced, BRAFV600-mutant melanoma who received anti-programmed cell death-1 (PD-1)/PD-L1 antibodies. We evaluated clinical outcomes, including objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) to initial and subsequent therapies in patients that received anti-PD-1 first (n=56) versus those that received BRAF±MEK inhibitors (BRAFi) first (n=58). Median OS was similar between these groups (27.5 vs. 40.3 mo, P=0.71). Patients who progressed on anti-PD-1 during the study timeframe had worse outcomes after starting subsequent BRAFi than those who had not received prior anti-PD-1 (median PFS 5 vs. 7.4 mo, median OS 10.6 vs. 40.3 mo). Similarly, patients who previously progressed on BRAFi had seemingly inferior outcomes after starting anti-PD-1 compared with those without prior BRAFi, including ORR (25% vs. 41%), median PFS (2.8 vs. 10.6 mo) and median OS (8.2 vs. 27.6 mo). Notably, patients who benefited >6 months from BRAFi had superior ORR to subsequent anti-PD-1 compared with those with more rapid progression (<6 mo) on BRAFi (34% vs. 15%, P=0.04). We conclude that either BRAFi or anti-PD-1 may be effective regardless of treatment sequence in patients with BRAFV600-mutant melanoma, but clinical outcomes to front-line therapy are superior. In addition, we suggest a shared "responder phenotype" between BRAFi and anti-PD-1.

Original languageEnglish (US)
Pages (from-to)31-35
Number of pages5
JournalJournal of Immunotherapy
Volume40
Issue number1
DOIs
StatePublished - Jan 1 2017

Keywords

  • BRAF
  • anti-PD-1
  • dabrafenib
  • immune
  • melanoma
  • nivolumab
  • pembrolizumab
  • sequence
  • trametinib
  • vemurafenib

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

Fingerprint Dive into the research topics of 'Sequencing Treatment in BRAF<sup>V600</sup> Mutant Melanoma: Anti-PD-1 before and after BRAF Inhibition'. Together they form a unique fingerprint.

Cite this