Dr. Weber on Optimal Therapy Sequences in Melanoma

Jeffrey S. Weber, MD, PhD, the director of the Donald A. Adam Comprehensive Melanoma Research Center at the Moffitt Cancer Center and Research Institute in Tampa, FL, discusses sequencing immunologic and targeted therapies in patients with advanced BRAF-mutated melanoma.

The current theory for patients with indolent or slow growing melanoma is to begin treatment with immunotherapy followed by a BRAF inhibitor. To test this theory, a retrospective study was conducted looking at patients with metastatic melanoma who had received immunotherapy followed by a BRAF inhibitor or the opposite sequence, explains Weber.

In this analysis, frontline treatment with a BRAF inhibitor resulted in a far worse outcome than immunotherapy. Moreover, Weber notes, those who received the immunotherapy first responded to BRAF inhibition just as well as those who received it in the frontline.

The results from this analysis need to be validated in a larger trial, Weber points out. However, at this point, it seems likely that patients who progress on a BRAF inhibitor may not have time to respond to immunotherapy. As a result, the optimal sequence appears to be immunotherapy upfront followed by BRAF or MEK/BRAF inhibition, Weber believes.