Quality of life in patients with BRAF-mutant melanoma receiving the combination encorafenib plus binimetinib: Results from a multicentre, open-label, randomised, phase III study (COLUMBUS)

Eur J Cancer. 2021 Jul:152:116-128. doi: 10.1016/j.ejca.2021.04.028. Epub 2021 Jun 4.

Abstract

Background: In COLUMBUS, treatment with encorafenib plus binimetinib in patients with advanced BRAF-mutant melanoma showed improved progression-free and overall survival with favourable tolerability compared to vemurafenib treatment. Here, results on health-related quality of life (HRQoL) are presented.

Methods: COLUMBUS was a two-part, open-label, randomised, phase III study in patients with BRAF-mutant melanoma. In PART-I, 577 patients were randomised (1:1:1) to encorafenib plus binimetinib, encorafenib or vemurafenib. The primary objective was to assess progression-free survival. As a secondary objective, HRQoL was assessed by the EQ-5D, the EORTC QLQ-C30 and the FACT-M questionnaires. Furthermore, time to definitive 10% deterioration was estimated with a Kaplan-Meier analysis and differences in mean scores between groups were calculated with a mixed-effect model for repeated measures. Hospitalisation rate and the impact of hospitalisation on HRQoL were also assessed.

Results: Patients receiving the combination treatment showed improvement of their FACT-M and EORTC QLQ-C30 global health status scores, compared to those receiving vemurafenib (post-baseline score differences: 3.03 [p < 0.0001] for FACT M and 5.28 [p = 0.0042] for EORTC QLQ-C30), indicative of a meaningful change in patient's status. Furthermore, a delay in the deterioration of QoL was observed in non-hospitalised patients compared to hospitalised patients (hazard ratio [95% CI]: 1.16 [0.80; 1.68] for EORTC QLQ-C30 and 1.27 [0.81; 1.99] for FACT-M) and a risk reduction of 10% deterioration, favoured the combination in both groups.

Conclusion: The improved efficacy of encorafenib plus binimetinib compared to vemurafenib, translates into a positive impact on the perceived health status as assessed by the HRQoL questionnaires. The study is registered with ClinicalTrials.gov, number NCT01909453 and EudraCT number 2013-001176-38.

Keywords: BRAF(V600E−K) mutant Melanoma; BRAF/MEK inhibitors Combination; Encorafenib plus binimetinib; Health-related quality of life; Hospitalisation rate.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Benzimidazoles / administration & dosage*
  • Benzimidazoles / adverse effects
  • Carbamates / administration & dosage*
  • Carbamates / adverse effects
  • Female
  • Humans
  • Male
  • Melanoma / drug therapy*
  • Melanoma / genetics
  • Melanoma / mortality
  • Melanoma / psychology
  • Middle Aged
  • Mutation
  • Progression-Free Survival
  • Proto-Oncogene Proteins B-raf / genetics
  • Quality of Life*
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / mortality
  • Skin Neoplasms / psychology
  • Sulfonamides / administration & dosage*
  • Sulfonamides / adverse effects
  • Vemurafenib / administration & dosage
  • Vemurafenib / adverse effects
  • Young Adult

Substances

  • Benzimidazoles
  • Carbamates
  • Sulfonamides
  • binimetinib
  • Vemurafenib
  • encorafenib
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf

Associated data

  • ClinicalTrials.gov/NCT01909453
  • EudraCT/2013-001176-38