Long-Term Real-World Outcomes and Safety of Vemurafenib and Vemurafenib + Cobimetinib Therapy in Patients with BRAF-Mutated Melanoma

Target Oncol. 2023 Mar;18(2):235-245. doi: 10.1007/s11523-023-00954-w. Epub 2023 Mar 11.

Abstract

Background: Combined treatment with BRAFi and/or MEK inhibitors (MEKi) improves outcomes in advanced melanoma patients in comparison with monotherapy.

Objective: We aim to report real-world treatment efficacy and safety of vemurafenib (V) and vemurafenib + cobimetinib (V + C) from 10 years of practice.

Patients and methods: A total of 275 consecutive patients with unresectable or metastatic BRAF mutated melanoma started first-line V or V + C treatment between 1 October 2013 and 31 December 2020. Survival analyses were performed using the Kaplan-Meier method, and Log-rank and Chi-square tests were used for comparison between groups.

Results: The estimated median overall survival (mOS) was 10.3 months in the V group, and 12.3 months in the V + C group (p = 0.0005; HR = 1.58, 95% CI 1.2-2.1), although the latter group of patients had lactate dehydrogenase elevated numerically more often. Estimated median progression-free survival (mPFS) was 5.5 months in the V group, and 8.3 months in the V + C group (p = 0.0002; HR = 1.62, 95% CI 1.3-2.1). Complete response, partial response, stable disease, and progressive disease as best responses were recorded in the V/V + C groups in 7%/10%, 52%/46%, 26%/28%, and 15%/16% of patients, respectively. The numbers of patients with any grade of adverse effects were similar in both groups.

Conclusions: We confirmed significant improvement in the mOS and mPFS of unresectable and/or metastatic BRAF mutated-melanoma patients treated outside clinical trials with V + C as compared with V, with no major increase in toxicity for the combination.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Humans
  • Melanoma* / drug therapy
  • Melanoma* / genetics
  • Melanoma* / pathology
  • Mutation
  • Proto-Oncogene Proteins B-raf / genetics
  • Skin Neoplasms* / drug therapy
  • Skin Neoplasms* / genetics
  • Vemurafenib / pharmacology
  • Vemurafenib / therapeutic use

Substances

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