More Enthusiasm for Newer Melanoma Therapies

In his talk, “Melanoma Guideline Update: New Agents and Opportunities for Treatment,” John A. Thompson, MD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington, first showed the preferred list of treatments for advanced or metastatic melanoma: ipilimumab, vemurafenib, dabrafenib, dabrafenib plus trametinib, high-dose interleukin-2, and the drugs-to-come in the category: “clinical trials.”

Then, Dr Thompson told the gathering at the National Comprehensive Cancer Network’s (NCCN) 19th annual conference—Advancing the Standard of Cancer Care—that, “Enthusiasm for older cytotoxic agents is waning very quickly,” a nod to the significant advances that have been made very recently—just in the past 3 years—including results presented last June at the annual meeting of the American Society of Clinical Oncology.

Dr Thompson was the final speaker at the opening day of the NCCN conference, on Thursday, March 13, 2014, in Hollywood, Florida.

Advances in metastatic melanoma treatments offer more hope than ever in this once-deadly disease. Treatment advances have not come without some rethinking of what constitutes progress, however, as the newer therapies work differently, and the pattern of delayed response has taken some adjusting for everyone involved. “We have to be patient and wait for the response,” Dr Thompson said.

Since the pair of studies that led to the approval of ipilimumab in the US in 2011, the therapy has been watched closely, especially since not all patients react to the drug the same way. And now that some time has elapsed since approval, and more results are in, there’s more that can be shared with patients about what to expect from the therapy, both with regards to outcomes and side effects.

“We have to be careful about toxicities,” Dr Thompson said. Just as response to therapy itself can vary, so can the side effects. “There can be a wide variation when they appear, but usually it’s about the second dose at about 3 weeks.” A wallet card can inform a caregiver or healthcare provider about what to expect, Dr Thompson said.

Ipilimumab is now being used as part of combination therapy, and it is far from the only modern option. Dr Thompson put his audience through multiple case scenarios, asking them to suggest treatment options, and the answers were scattered. An interesting slide came late in the presentation, when Dr Thompson showed results from Ribas et al, a 2012 article in Clinical Cancer Research,¹ which seemed to show more robust results early on for targeted therapies in melanoma, but better long-term results for immunotherapy.

What does Dr Thompson see ahead in immunotherapy and targeted therapy for melanoma? In immunotherapy, he sees progress in (1) new immune checkpoint inhibitors, such as anti-PD-1s; (2) T-cell therapy, including cells with engineered immune-recpetors; (3) lymphokins such as IL-15 and IL-21, alone or in combination with vaccines or checkpoint inhibitors; and (4) receptor-directed cytokines.

In targeted therapy, look for (1) “molecularly targeted” agents, such as MEK inhibitors; (2) studies of the mechanisms of acquired resistance to targeted agents; and (3) combinations of targeted agents with immunomodulators, which regulate the skin’s immune response.

REFERENCE

1. Ribas A, Hersey P, Middleton MR, et al. New challenges in endpoints for drug development in advances melanoma. Clin Cancer Res. 2012;18:336-341.