Researchers report that it may be possible to cure some patients with metastatic melanoma, but only if there is a dramatic shift in collaboration among clinicians and scientists. Writing in the Lancet Oncology, they argue that to achieve cures with this disease, researchers must better understand the interplay between host and tumor factors; such an understanding will necessarily involve international collaboration.1 Local collaboration is needed by community oncologists, clinical researchers, and translational researchers.
“Newly diagnosed patients with unresectable, metastatic melanoma still need to participate in appropriate clinical trials. We’re not quite at a place where every patient with a BRAF mutation will receive targeted therapy as his or her first and hopefully only treatment,” said co-author Vernon Sondak, MD, chair of the department of cutaneous oncology at Moffitt Cancer Center, professor at oncologic sciences, and director of surgical education at the University of South Florida’s College of Medicine in Tampa.
“Major questions remain about which melanoma patients should be treated with targeted therapy, not which ones should receive immunotherapy. That’s what we need to determine through additional clinical trials combined with translational research: we need better understanding of the tumor and patient factors that determine response.”
The authors write that the past 5 years have been changed the melanoma treatment landscape, with the approval of several molecularly targeted or immunotherapy treatments that meaningfully improve outcomes for patients with metastatic disease.
Others researchers have reported positive findings in the extended follow-up results of the coBRIM phase 3 trial. The combination of the MEK inhibitor cobimetinib and the BRAF inhibitor vemurafenib was evaluated for patients with previously untreated BRAFV600-mutant metastatic melanoma. The latest follow-up showed a significant improvement in progression-free survival (PFS) when vemurafenib was added to cobimetinib, in contrast with vemurafenib plus placebo.2
“This was a very well done clinical trial and strongly supports the use of combination BRAF/MEK inhibitor therapy when using molecularly-targeted therapy. The side effects are clearly manageable and acceptable to patients with advanced melanoma. While it doesn’t break new ground or tell us which BRAF/MEK combination is better, it does show that some patients can have long-lasting benefits from treatment,” Dr Sondak told Cancer Therapy Advisor.
Douglas Johnson, MD, assistant professor of medicine and the clinical director of melanoma at Vanderbilt University in Nashville, Tennessee, said that the treatment landscape is changing for patients with metastatic melanoma. A number of different receptors that either stimulate or inhibit the immune response to the tumor have been characterized, and are being exploited with novel therapies.
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“Current clinical trials are testing many of these agents. The largest barriers are that we still do not understand the importance of each individual component of the immune system, and we have not yet characterized the specific antigens that the immune system recognizes,” Dr Johnson told Cancer Therapy Advisor.
According to Dr Johnson, clinical practice has dramatically changed with the approval of anti-PD-1 agents in numerous cancers, and with the approval of combination immunotherapy and oncolytic viral therapy for melanoma. And there is more reason than ever for optimism, due to the large numbers of immune therapy trials now underway. In the not-too-distant future, several new combination therapies are expected, and they should represent an improvement not only in effectiveness, but in safety as well.
- Khushalani NI, Sondakemail VK. Are we there yet? Prolonged MAPK inhibition in BRAFV600-mutant melanoma. Lancet Oncol. 2016 Jul 29. doi: 10.1016/S1470-2045(16)30368-0 [Epub ahead of print]
- Ascierto PA, McArthur GA, Dreno B, et al. Cobimetinib combined with vemurafenib in advanced BRAFV600-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol. 2016 Jul 29. doi: 10.1016/S1470-2045(16)30122-X [Epub ahead of print]