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.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Benzimidazoles/administration & dosage , Carbamates/administration & dosage , Melanoma/drug therapy , Quality of Life , Skin Neoplasms/drug therapy , Sulfonamides/administration & dosage , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Benzimidazoles/adverse effects , Carbamates/adverse effects , Female , Humans , Male , Melanoma/genetics , Melanoma/mortality , Melanoma/psychology , Middle Aged , Mutation , Progression-Free Survival , Proto-Oncogene Proteins B-raf/genetics , Skin Neoplasms/genetics , Skin Neoplasms/mortality , Skin Neoplasms/psychology , Sulfonamides/adverse effects , Vemurafenib/administration & dosage , Vemurafenib/adverse effects , Young AdultABSTRACT
INTRODUCTION: Pre-treatment of the skin to remove scales and crusts prior to photodynamic therapy (PDT) is essential to enhance the uptake of topically applied methyl aminolevulinate (MAL) and to improve treatment efficacy. This study compared the effect of two different skin preparation pads on skin integrity in ex vivo human skin. METHODS: Ex vivo human skin samples from three donors were pre-treated in triplicates with PREPSTER™ (PR) skin preparation pad (6, 8, and 10 passages) or Ambu Unilect™ (A-UN) skin preparation pad (6, 8, and 10 passages). In addition, skin samples were pre-treated with tape strippings (10 adhesive tape strips) as a reference method for comparison. Transepidermal water loss (TEWL) was measured on intact skin and following skin barrier impairment using skin preparation pads and tape stripping. Histological analysis was performed to verify the impairment of the stratum corneum (SC) barrier function in samples from intact skin (control), 10 tape strippings (reference method), 10 passages of PR, and 10 passages of A-UN. RESULTS: TEWL increased with the increasing number of passages of skin preparation pads, with 2.4- and 3.3-fold increases following 10 passages of A-UN and PR, respectively, versus a 2.2-fold increase with 10 tape strippings (reference). Histological analysis showed only partial removal of the SC, with no damage observed on the epidermis, regardless of the procedure used. CONCLUSION: Pre-treatment of skin using PR and A-UN skin preparation pads markedly increases TEWL, indicating slight impairment of the SC barrier function. Comparison of both skin preparation pads showed that PR pad consistently induced significantly higher TEWL than A-UN pad (p < 0.05), regardless of the number of passages. Both skin preparation pads are thought to increase the uptake of MAL and can therefore be used for the preparation of skin prior to PDT. FUNDING: Nestlé Skin Health - Galderma R&D.
