Outcomes in patients with BRAF V600 -mutated melanoma and brain metastases at baseline treated with dabrafenib plus trametinib.

Background: Brain metastases (BM) and lactate dehydrogenase (LDH) levels above the upper limit of normal (ULN) are associated with poor prognosis in patients with melanoma. Although treatment with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib have demonstrated long-term clinical benefit in patients with melanoma, data on their efficacy in patients with BM are limited.
Methods: DESCRIBE Italy is an observational, retrospective, real-world study evaluating dabrafenib plus trametinib in 499 patients with BRAF ^V600 -mutant stage III unresectable or stage IV melanoma from various sites across Italy. Here, we analyzed the clinical outcomes for the subgroup of patients receiving first-line treatment and presenting with BM at diagnosis and assessed the impact of predictive factors such as LDH levels and the presence of other metastases on median progression-free survival (mPFS).
Results: Overall, 325 evaluable patients were on first-line therapy and are the focus of this analysis; of these, 76 patients (23.4%) had BM at baseline. mPFS was lower for patients with BM at baseline compared with overall patients (8.7 months vs 9.3 months, respectively). Patients with BM at diagnosis and LDH >ULN had a considerably shorter mPFS compared with patients with LDH ⩽ULN (5.3 months vs 9.9 months, respectively). mPFS was noticeably longer for patients with cerebral metastases only compared with patients with cerebral and other metastases (15.0 months vs 8.7 months, respectively).
Conclusions: Dabrafenib plus trametinib showed effectiveness in a real-world population of patients with advanced BRAF ^V600 -mutated melanoma and BM at baseline, supporting its use in this population with poor outcomes.
Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MA has received research funding from AstraZeneca and Pharmamar; has received consulting fees from Bayer, BMS, Merck and Novartis; and has received travel support from BMS, Merck and Tesaro. VC-S has received honoraria from MDS, Merck Serono and Novartis; has received travel support from BMS, Novartis and Pierre Fabre; and has participated in advisory boards for Pierre Fabre. MGuidoboni has received consulting fees from BMS and Novartis; has received honoraria from BMS and Pierre Fabre; has received travel support from Pierre Fabre; and has participated in advisory boards for BMS. RD has received honoraria from BMS, MSD, Novartis, Pierre Fabre and Sanofi. AM has received honoraria from Merck, Pierre Fabre and Sun Pharma, and has participated in advisory boards for BMS, MSD, Novartis and Pierre Fabre. FC has received honoraria from BMS, Merck, Novartis and Pierre Fabre, and has participated in advisory boards for BMS, Merck and Novartis. PAA has received research funding from BMS, Pfizer, Roche-Genentech and Sanofi; has received consulting fees from 4SC, AstraZeneca, BMS, Boehringer-Ingelheim, Daiichi Sankyo, Eisai, Idera, Immunocore, Italfarmaco, iTeos, Lunaphore, Merck Serono, Merck Sharp & Dohme, Nektar, Nouscom, Novartis, Oncosec, Pfizer, Pierre Fabre, Regeneron, Roche-Genentech, Sandoz, Sanofi, Seagen and Sun Pharma; and has received travel support from MSD. RM has received consulting fees from BMS, Ipsen, MSD, Novartis and Pierre Fabre; has received honoraria from BMS, Ipsen, MSD, Novartis, Pierre Fabre and Sanofi; has received travel support from BMS, Ipsen, MSD and Novartis; has participated in advisory boards for BMS, Ipsen, MSD, Novartis and Pierre Fabre. VF has received honoraria from BMS, MSD, Novartis and Pierre Fabre; has received travel support from BMS and Pierre Fabre; and has participated in advisory boards for BMS, MSD and Novartis. MT has received institutional research funding from Novartis; has received honoraria from BMS, Novartis and Pierre Fabre; has received travel support from MSD; and has participated in advisory boards for Novartis. GT has received honoraria from Molteni, Novartis and Pharmamar. MGuida has participated in advisory boards for BMS, Merck, Novartis and Pierre Fabre. MDV has received consulting fees from BMS, Merck, Novartis, Pierre Fabre and Sanofi; has received honoraria from BMS, Merck, Novartis, Pierre Fabre and Sanofi; has received travel support from BMS, Merck, Novartis, Pierre Fabre and Sanofi; and has participated in advisory boards for BMS, Merck, Novartis, Pierre Fabre and Sanofi. IGM is a Novartis employee. PQ has received consulting fees from BMS, Merck, Novartis, Pierre Fabre, Roche and Sanofi; has received honoraria from BMS, Merck, Novartis, Pierre Fabre, Roche and Sanofi; has received travel support from BMS, Merck, Novartis, Pierre Fabre, Roche and Sanofi; and has participated in advisory boards for BMS, Merck, Novartis, Pierre Fabre, Roche and Sanofi. MB, PF, RG, GLR, and GR have no conflict of interest to declare.