Dr. Jason Luke on Sequencing Targeted and Immunotherapy Agents in BRAF+ Melanoma

Jason Luke, MD, an assistant professor of Medicine at the University of Chicago Medicine, discusses the role for immunotherapy and targeted agents in patients with BRAF-positive melanoma.

Both BRAF-targeted agents and immunotherapies have been shown to improve overall survival in this patient population, says Luke. However, it is important to sequence these agents in a smart manner, he says. To date they have only been used individually, and the standard of care is still to use them until progression, and then use the next one—whether it be a BRAF inhibitor and then immunotherapy, or vice versa. The best approach is unknown, says Luke.

There are some phase I clinical trials that are now starting to be reported in which all of these drugs are being given at once, including BRAF and MEK inhibitors plus PD-1 antibodies. The rationale for doing that is not totally clear, says Luke. These are the questions we need to sort out. Using multi-dimensional biomarker analysis, it will be possible to eventually hone in on which patients will derive the most benefit, he says.

However, resistance is a concern. Unfortunately, some overlapping phenotypes between targeted therapy and immunotherapy have been found. This is a little bit disconcerting because that could suggest that the patients most likely to benefit from targeted therapy are also those who are most likely to benefit from immunotherapy, says Luke. If all are given at once and resistance occurs, then the patient could be resistant to everything. This is still being investigated.