Retrospective review of outcomes associated with metastatic melanoma patients treated with 1st-line BRAF-targeted therapy

Pigment Cell Melanoma Res. 2022 Nov;35(6):595-604. doi: 10.1111/pcmr.13067. Epub 2022 Sep 25.

Abstract

BRAF-mutant melanoma patients can theoretically access both immunotherapy and BRAF-targeted therapy as treatment for metastatic disease. BRAF-targeted therapy is increasingly used 1st line for poorer prognostic patients, so we wanted to assess realistic expectations of these patients accessing 2nd-line immunotherapy. We conducted a retrospective review of clinical outcomes in 25 patients treated over the last 3 years with 1st-line BRAF-targeted therapy in a real-world clinical setting at a UK-based tertiary centre. Compared with the registration trials, our patients receiving 1st-line BRAF-targeted therapy had poorer performance status, higher disease burden, shorter median progression-free survival (5.05 months, 95% CI: 3.96-8.88) and shorter median overall survival (11.5 months, 95% CI: 6.24 - not reached). Overall response rate was similar, at 64%. On disease progression, median survival was 2.34 months (95% CI: 1.62 - not reached). Only five patients went on to receive 2nd-line immunotherapy. Metastatic melanoma patients treated with 1st-line BRAF-targeted therapy now have different demographics compared with those recruited to registration trials conducted over the last 10 years. In a modern-day, real-world setting, these patients should be counselled that only 1 in 5 are likely to receive 2nd-line immunotherapy and their survival times are expected to be short.

Keywords: BRAF; dabrafenib; encorafenib; immunotherapy; melanoma.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Humans
  • Immunotherapy
  • Melanoma* / pathology
  • Molecular Targeted Therapy
  • Mutation / genetics
  • Neoplasms, Second Primary*
  • Proto-Oncogene Proteins B-raf / genetics
  • Retrospective Studies
  • Skin Neoplasms* / drug therapy
  • Skin Neoplasms* / pathology

Substances

  • Proto-Oncogene Proteins B-raf
  • BRAF protein, human