Combinations Are the Future for Metastatic Melanoma Treatment

The treatment landscape for metastatic melanoma has drastically changed over the years and will continue to evolve as more study results come out, according to Dr. Allison Betof Warner, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City.

“In the trial space, we're seeing combinations upon combinations, which are really exciting. There are combinations of almost every type of other therapy that hopefully we can finally bring to the melanoma space,” she said in an interview with OncLive, a sister publication of CURE.

COMBI-I Trial

Warner expressed particular excitement for findings of the COMBI-i trial, which is examining the PD-1 inhibitor spartalizumab plus Tafinlar (dabrafenib) and Mekinist (trametinib) in previously untreated patients with advanced BRAF V-600—mutant melanoma.

“Of course we're waiting on final analysis, but the data that came out [from the COMBI-i trial], at ASCO were really promising and really exciting,” she said. “We're all waiting with unbated breath to see the final analyses. But I think there are numerous other combinations that are coming, of targeted therapy, and not just BRAF/MEK targeted therapy. I think that's exciting.”

About 40% of patients on the trial had a complete response (CR), meaning “the disappearance of all signs of cancer in response to treatment,” according to the National Cancer Institute (NCI). Warner also added that the responses are durable, which is promising since, in the past, targeted therapy tended to have high response rates, but they did not last.

Researchers on the trial were also concerned with the side effect profile of the combination, knowing that there could be some overlapping toxicities between the two agents. However, Warner said that most patients tolerated the regimen fairly well.

“We're really looking forward to seeing the final data, but I think it's really promising. We're going to see more and more of these combinations coming,” Warner said.

The Future of Treatment

Looking ahead, Warner said that there may be potential for four-drug regimens in the future, namely BRAF/MEK inhibitors plus anti-PD-1/CTLA-4 agents.

“[We're looking forward to] truly novel combinations as well. The combination of axitinib plus PD-1 really opens the door to these other targets that we haven't been seeing in melanoma for a long time. I think we're going to see more of that as well, not just in the VEGF or TKI space, but a variety of targets. We're seeing HDAC inhibitors and things like that in trials as well,” she said.

Overall, the space is moving toward more combination therapies. “In the trial space, we're seeing combinations upon combinations, which are really exciting. There are combinations of almost every type of other therapy that hopefully we can finally bring to the melanoma space.”