New drugs are rapidly changing the treatment paradigm for stage IV melanoma, but there is still validity to some of the old standbys, according to Michael Sabel, MD, of the University of Michigan, Ann Arbor, who described the shifting landscape of melanoma treatment at the Best of ASCO Boston meeting.

He reminded attendees that for otherwise healthy patients, interleukin (IL)-2 produces durable responses in a small percentage of patients. “We are so caught up in talking about BRAF inhibitors for BRAF-mutated tumors and the anti-CTLA4 antibody ipilimumab for wild-type BRAF, but we don’t want to forget about this,” he said. For less healthy patients, dacarbazine is often still appropriate.

Surgery as well remains a prominent player in metastatic disease, with complete resection of tumors yielding long-term survival in as many as 40% of properly selected patients. “Any patient who is potentially surgically resectable should be evaluated for resection,” said Dr. Sabel, who is an oncologic surgeon. “What will be interesting is defining the role of surgery as new agents become incorporated.”

Future Combinations

“Treatment choices have certainly become more confusing,” he said. Looking ahead, he maintained that IL-2 will still be a consideration, as will surgery, in many patients. When combined with the gp100 vaccine, IL-2 responses improve, he noted.

“IL-2 may see resurgence in the future as more data emerges about combining it with vaccines,” he predicted, adding that the use of a vaccine with anti-PD1 or ipilimumab “to generate a novel immune response, then take the brakes off with the others” is, at least theoretically, another interesting idea.

For patients with BRAF-mutated melanoma, dabrafenib joins vemurafenib in the growing arsenal of agents against these tumors and should prove extremely valuable in patients with brain metastases, he said. He added that dabrafenib will probably not be positioned as a drug to use after vemurafenib resistance emerges. “This is not intrinsically logical,” he pointed out. 

The combination of dabrafenib and the MEK inhibitor trametinib is very exciting, Dr. Sabel noted, largely due to the lower risk for skin toxicity observed with this combination. “Combination therapy is where we are going, not just for higher response rates but for almost eradicating squamous cell carcinomas,” he commented. ■

Disclosure: Dr. Sabel reported no potential conflicts of interest.