Immunotherapies and the Challenge They Present in Melanoma

With the field of immunotherapy growing at a rapid rate, and its increasing incorporation in the armamentarium of treatments in melanoma, Jeffrey S. Weber, MD, PhD, discusses where the field is going and how oncologists can be using the therapies.

Jeffrey S. Weber, MD, PhD

With the field of immunotherapy growing at a rapid rate, and its increasing incorporation in the armamentarium of treatments in melanoma, Jeffrey S. Weber, MD, PhD, discusses where the field is going and how oncologists can be using the therapies.

“When I first got into immunotherapy in cancer, the field didn’t have a lot of respect,” says Weber, MD, PhD, deputy director, Laura and Isaac Perlmutter Cancer Center, co-director of its Melanoma Program, head of Experimental Therapeutics, NYU Langone Medical Center. “It took until the last few years when checkpoint inhibitors became a new modality with success in many different cancers, for everyone in the field to accept the fact that immunotherapy was here to stay.”

This coming integration of immunotherapies into melanoma essentially means oncologists must also wear an "immunotherapist" hat as well, according to Weber. Doubly so considering melanomas are the first type of tumor to adopt the use of immunotherapies. Despite the newness of the treatment, oncologists have a lot to learn, he added.

With the constant advances in immunotherapy, Weber hopes to eventually replace chemotherapy as a treatment in melanoma and drop the treatment much lower in the hierarchy.

"In our field, I do think immunotherapy will essentially replace the use of chemotherapy. I think it will drop to a fourth- or fifth-choice therapy. Chemotherapy will not disappear entirely. It will still have a place as a debulking modality and as an adjuvant therapy in breast cancer, colon cancer, and others," he said."

"I look forward to the day when we will no longer have to deal with myelosuppression, mucositis, and all of the horrible manifestations from cytotoxic chemotherapy. It is not going to happen soon, but I think it will happen in my working lifespan."

Outside the treatment's inherent competition with chemotherapy as a leading treatment in melanoma, within the field of immunotherapies themselves lie additional races to the top. Weber says there are currently ongoing trials to address the issue.

"Interestingly, the most important trial that addresses issues of targeted versus immunotherapy is a large randomized cooperative group trial that NYU Langone will be part of, which randomly allocates BRAF-mutated patients with metastatic melanoma to either receive initial targeted therapy with the BRAF-targeted drugs daratumumab (Darzalex) and trametinib (Mekinist) followed by ipilimumab (Yervoy) and nivolumab (Opdivo) when they fail, or they start with ipilimumab and nivolumab and then receive daratumumab and trametinib if they fail," he said.

In February 2015, nivolumab (Opdivo) as both a single-agent and in combination ipilimumab (Yervoy) was expanded in its approval by the FDA to include patients with BRAF V600 mutations. The drug was originally approved by the FDA for advanced melanoma in November 2015.

Weber says despite these ongoing trials, it would be too difficult to determine how long to prime a patient with a targeted therapy before switching to an immunotherapy. He adds that even without this definitive information stemming from a hypothetical trial, oncologists should be tailoring treatment to each patient to determine which works best.