Association of programmed death ligand-1 (PD-L1) expression with treatment outcomes in patients with BRAF mutation-positive melanoma treated with vemurafenib or cobimetinib combined with vemurafenib

Pigment Cell Melanoma Res. 2018 Jul;31(4):516-522. doi: 10.1111/pcmr.12670. Epub 2017 Dec 10.

Abstract

The prognostic significance of programmed death ligand-1 (PD-L1) on treatment outcomes in patients receiving BRAF with or without MEK inhibitors is not well understood. This retrospective exploratory analysis evaluated the association of tumour PD-L1 expression with progression-free survival (PFS) and overall survival (OS) among 210 patients in the coBRIM trial treated with cobimetinib plus vemurafenib or placebo plus vemurafenib. In the vemurafenib cohort, there was a trend of increased PFS and OS in those with PD-L1+ melanoma, with hazard ratios (HRs; PD-L1+ vs. PD-L1- ) of 0.70 (95% CI, 0.46-1.07) and 0.69 (95% CI, 0.42-1.13) for PFS and OS, respectively. However, in patients treated with cobimetinib plus vemurafenib, a similar trend was not observed with HRs (PD-L1+ versus PD-L1- ) of 1.04 (95% CI, 0.66-1.68) and 0.94 (95% CI, 0.57-1.57) for PFS and OS, respectively. The combination cobimetinib plus vemurafenib appears to overcome the poor prognosis associated with low PD-L1 expression.

Keywords: cobimetinib; immunohistochemistry; melanoma; prognosis; programmed death ligand-1; vemurafenib.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Azetidines / administration & dosage
  • B7-H1 Antigen / biosynthesis*
  • B7-H1 Antigen / genetics
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Melanoma* / drug therapy
  • Melanoma* / genetics
  • Melanoma* / metabolism
  • Melanoma* / mortality
  • Middle Aged
  • Mutation*
  • Piperidines / administration & dosage
  • Proto-Oncogene Proteins B-raf* / genetics
  • Proto-Oncogene Proteins B-raf* / metabolism
  • Survival Rate
  • Vemurafenib / administration & dosage

Substances

  • Azetidines
  • B7-H1 Antigen
  • CD274 protein, human
  • Piperidines
  • Vemurafenib
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • cobimetinib