Long-Term Survival Possible With MAPK Inhibition in BRAF-Mutant Melanoma

July 30, 2015

Results of a study suggest that durable survival is possible in melanoma patients treated with MAPK inhibitors, and is perhaps similar to the survival observed with ipilimumab.

Long-term outcomes for BRAF-mutant melanoma patients treated with BRAF and MEK inhibitors are influenced by a number of baseline factors including BRAF genotype, gender, and serum lactate dehydrogenase (LDH) levels, according to a new study.

Treatment of V600 BRAF-mutant metastatic melanoma has improved with inhibition of the MAPK pathway with BRAF inhibitors and MEK inhibitors. But “the degree of response and the duration of survival are highly variable,” wrote study authors led by Alexander M. Menzies, MBBS, of the Melanoma Institute Australia in Sydney. “Whether clinicopathologic factors can be used to predict the clinical course of these patients is largely unknown, and there have been few studies examining this issue.”

The study included 142 consecutive immunotherapy- and MAPK inhibitor–naive patients with BRAF-mutant metastatic melanoma. All were treated either with BRAF inhibitors (111 patients) or with a combination of dabrafenib and trametinib (31 patients), and the median follow-up was 15.7 months. Results were published online ahead of print in Cancer.

The 2-year survival rate for the full cohort was 43%; at 3 years the rate was 24%, and at 4 years it was again 24%. The response rate for the group was 70%, with 5% achieving a complete response, 65% with a partial response, and 24% with stable disease.

Several factors were found on multivariate analysis to be associated with longer overall survival (OS). These included female gender, with a hazard ratio (HR) of 0.61 (P = .026), and normal LDH levels, with an HR of 0.31 (P < .001). In patients with normal LDH levels the median OS was 23.5 months, compared with only 7.3 months in those with elevated LDH levels.

The same two factors were associated with longer progression-free survival, as well as the BRAF V600E genotype, with an HR of 0.51 (P = .006), and treatment with dabrafenib and trametinib, with an HR of 0.60 (P = .048).

“The results of this study suggest that durable survival is possible with MAPK inhibitors and that this survival is perhaps similar to that observed with ipilimumab, especially in patients with low LDH levels,” the authors concluded. “The clinicopathologic correlates of MAPK inhibitor outcomes described here (particularly serum LDH) warrant validation in larger series and may help to inform therapeutic decisions in the future.”