Using biomarkers to predict response to combination therapies in BRAF-mutant melanoma

Grant McArthur, MBBS, BMedSci, PhD, FRACP, of the Peter MacCallum Cancer Centre, Melbourne, Australia, discusses the two currently approved combination therapies used for treating BRAF-mutant melanoma. First we have dabrafenib with trametinib and second, cobimetinib with vemurafenib, a BRAF and MEK inhibitor, which are currently the standard of care for melanoma.
Prof. McArthur describes the recent understanding of subsets of patients that may do better or worse with the approach of dual approaches in treating tumors. He explains that researchers are now learning that patients with an elevated lactate dehydrogenase (LDH) level, have poor progression-free survival (PFS) and overall survival (OS). He highlights that this represents very important data now as it is important to select a patient population that is not going to do well, as alternative therapies need to be found for such populations of patients.
There are additional markers, such as the number of metastatic sites, and the number of liver metastases, are predictive of poor outcome. The influence of a patient’s’ performance status is also quite significant in such studies. If a patient has a performance status of 1, where there are symptoms related to the disease, where the lactate dehydrogenase is high, for example, such patients do very poorly with the targeted therapies, and innovation needs to occur. He suggests that perhaps the combination therapy of CTLA-4/PD-1 is the way to go at the moment for these patients, and great anticipation lies within the analysis of dividing up metastatic melanoma into subsets for the immunotherapy as well as targeted therapies in order to identify different subsets of patients and optimize the treatment choices available for such patients.
Recorded at the 2016 World Congress on Cancers of the Skin (WCCS) and the Congress of the European Association of Dermato-Oncology (EADO) in Vienna, Austria.

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