Emerging Approaches for BRAF-Mutant Metastatic Melanoma

Source: OnClive, July 2019


Geoffrey Thomas Gibney, MD: In patients with BRAF-mutated melanoma, as well as melanoma in general that is advanced and unresectable, we’ve made major progress in the treatment strategies. However, there still are major hurdles, major unmet needs. Currently, we do not know how to select patients very precisely for the therapy that we offer. The BRAF genotyping is very important for selecting patients who would benefit from BRAF-targeted therapy. But even within that population of patients, there are patients with BRAF mutations that respond very well or less well. And we really need to be able to sort out those patients better ahead of time, so we can have better discussions with patients and maybe even develop the therapeutic approach better. Or if we know that they have a BRAF mutation but are predicted to have a poor response to BRAF-targeted therapy, that may be a patient that you would offer immunotherapy first, and vice versa, the same would be true.

We have been able to identify resistance mechanisms for BRAF-targeted therapy as well as immunotherapies. There has been some investigation into looking at these as markers to predict who would have a better response or predictive model. It’s still very early and has not been very successful to the point where we can use it in routine clinical practice. What we’re lacking are prospective studies with a biomarker that is used to select patients to guide a treatment, and hopefully we will get there soon. And this will really make a major improvement in the way we treat patients and their outcomes.

Ryan J. Sullivan, MD: What’s clear about the field with targeted therapy, particularly BRAF-targeted therapy in melanoma, is we’re not there yet in terms of having therapies that work for the great majority of our patients. They work for the great majority of our patients, but they only work for a relatively short period of time for most of those patients. And so what we’d really like to be able to do is develop more robust strategies that target the MAP [mitogen-activated protein] kinase pathway but potentially other targets in cancer cells that might lead to more prolonged and deeper responses in our patients just with targeted therapy.


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