Extended Follow-Up Supports Dabrafenib Plus Trametinib in Metastatic BRAF-mutated Melanoma

Three-year survival results support dabrafenib plus trametinib for the treatment of BRAF V600-positive metastatic melanoma

medwireNews: Extended follow-up suggests a median overall survival (OS) of at least 2 years for patients given dabrafenib plus trametinib for BRAFV600 mutation-positive metastatic melanoma.

And a fifth of patients were free from progressive disease after 3 years, the authors report in the Journal of Clinical Oncology.

“The combination has an acceptable long-term safety profile and is a standard of care for patients with BRAFmutation–positive metastatic melanoma, particularly given the recent publications demonstrating a significant improvement in the PFS [progression-free survival] and OS in phase III trials of combination versus single-agent BRAF inhibitors”, emphasize Georgina Long, from The University of Sydney in New South Wales, Australia, and co-workers.

The study included data for 54 patients who were randomly assigned to receive the BRAFinhibitor dabrafenib plus the MEK inhibitor trametinib in a clinical trial, and a further 24 patients who received the same treatment in a non-randomised setting.

The patients, who were all BRAF inhibitor-naive, received dabrafenib 150 mg twice daily plus trametinib 2 mg once daily and were followed-up for a median of 45.6 and 47.1 months in the randomised and non-randomised groups, respectively.

In the randomised group, OS was a median of 25.0 months with 1-, 2- and 3-year OS rates of 80%, 51% and 38%, respectively, and corresponding PFS rates of 41%, 25% and 21%.

And for the non-randomised patients, OS was a median of 27.4 months with OS rates at 1, 2 and 3 years of 72%, 60% and 47%, respectively. PFS for these time points was 44%, 22% and 18%, respectively.

The researchers note that patients with prolonged OS or lack of RECIST progression shared the baseline characteristic of a normal lactate dehydrogenase level, as well as earlier stage disease and fewer metastatic organ sites than patients with poorer outcomes.

They summarise that the markers are all “factors associated with low-volume disease—classically considered a hallmark for front-line immunotherapy.”

In addition, a RECIST complete response was associated with a trend towards prolonged OS, but did not preclude recurrence, the researchers comment.

“It should be noted that although this study reports the longest follow-up data for patients treated with targeted therapies, the analyses were limited by small numbers of patients; thus, phase III trials of targeted therapies and newer immunotherapies (eg, PD-1/PD-L1 axis inhibitors) will help clarify the predictive versus prognostic nature of the baseline factors”, they say.

“The need to develop specific predictive molecular markers for each therapy is now even more compelling.”


Long GV, Weber JS, Infante JR, et al. Overall survival and durable responses in patients with BRAF V600-mutant metastatic melanoma receiving dabrafenib combined with trametinib. J Clin Oncol 2016; Advance online publication 25 January. doi: 10.1200/JCO.2015.62.9345

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