First-line BRAF/MEK inhibitors versus anti-PD-1 monotherapy in BRAFV600-mutant advanced melanoma patients: a propensity-matched survival analysis

Br J Cancer. 2021 Mar;124(7):1222-1230. doi: 10.1038/s41416-020-01229-1. Epub 2021 Jan 26.

Abstract

Background: Anti-PD-1 antibodies and BRAF/MEK inhibitors are the two main groups of systemic therapy in the treatment of BRAFV600-mutant advanced melanoma. Until now, data are inconclusive on which therapy to use as first-line treatment. The aim of this study was to use propensity score matching to compare first-line anti-PD-1 monotherapy vs. BRAF/MEK inhibitors in advanced BRAFV600-mutant melanoma patients.

Methods: We selected patients diagnosed between 2014 and 2017 with advanced melanoma and a known BRAFV600-mutation treated with first-line BRAF/MEK inhibitors or anti-PD-1 antibodies, registered in the Dutch Melanoma Treatment Registry. Patients were matched based on their propensity scores using the nearest neighbour and the optimal matching method.

Results: Between 2014 and 2017, a total of 330 and 254 advanced melanoma patients received BRAF/MEK inhibitors and anti-PD-1 monotherapy as first-line systemic therapy. In the matched cohort, patients receiving anti-PD-1 antibodies as a first-line treatment had a higher median and 2-year overall survival compared to patients treated with first-line BRAF/MEK inhibitors, 42.3 months (95% CI: 37.3-NE) vs. 19.8 months (95% CI: 16.7-24.3) and 65.4% (95% CI: 58.1-73.6) vs. 41.7% (95% CI: 34.2-51.0).

Conclusions: Our data suggest that in the matched BRAFV600-mutant advanced melanoma patients, anti-PD-1 monotherapy is the preferred first-line treatment in patients with relatively favourable patient and tumour characteristics.

Publication types

  • Comparative Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Follow-Up Studies
  • Humans
  • Longitudinal Studies
  • MAP Kinase Kinase 1 / antagonists & inhibitors*
  • Male
  • Melanoma / drug therapy
  • Melanoma / genetics
  • Melanoma / mortality*
  • Melanoma / pathology
  • Middle Aged
  • Mutation*
  • Prognosis
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Propensity Score
  • Prospective Studies
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors
  • Proto-Oncogene Proteins B-raf / genetics*
  • Survival Rate
  • Young Adult

Substances

  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Protein Kinase Inhibitors
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human