Combined therapy with dabrafenib and trametinib in BRAF-mutated metastatic melanoma in a real-life setting: the INT Milan experience

Purpose: Combination therapy with dabrafenib and trametinib is safer and more effective than BRAF inhibitor-based monotherapy for metastatic melanoma. Methods: We retrospectively analyzed BRAF-mutated metastatic melanoma patients treated at our institution with daily oral dabrafenib 300 mg and trametinib 2 mg from November 2013 to April 2016. This clinical record included both untreated and previously treated stage IV melanomas. Physical examination and laboratory examinations were performed monthly and disease re-evaluations were performed every 3 months. Results: A total of 48 patients (24 male, 24 female) with BRAF-mutated metastatic melanoma received dabrafenib and trametinib; median age was 48 years (range 23-75). Median follow-up was 362.5 days (range 72-879). Best overall response rate consisted of 6.2% (3 patients) complete response, 64.6% (31) partial response, and 25% (12) stable disease; median time to best response was 11 weeks (range 5.7-125.5). Progression of disease was seen in 19 patients (39.6%), with median time to progression (TTP) of 26 weeks (range 8-54). A total of 15 patients (31.2%) died due to progression of disease. Median progression-free survival and median overall survival were not reached. To date, 30 patients (62.5%) are still under treatment. A total of 27 (56.2%) patients had at least one adverse event (AE); grade 3-4 AEs were seen in 4 cases (8.3%). The main toxicities were fever (25%), skin rash (14.6%), arthralgias (10.4%), and aspartate aminotransferase/alanine aminotransferase increase (8.3%). Treatment dose was reduced in 7 subjects (14.6%), with only one case of discontinuation due to AE. Conclusions: Our data, using combined targeted therapy, are in line with the scientific literature in terms of both safety and effectiveness in a real-life setting.