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NCCN 2016

NCCN Melanoma Guideline Update: It's About Immunotherapy and Targeted Therapy

Surabhi Dangi-Garimella, PhD
At the National Comprehensive Cancer Network 21st Annual Conference, John A. Thompson, MD, presented an update on where the field of melanoma treatment stands today.
Immune checkpoint inhibitors, successful combination therapy approaches, oncolytic virus—treatment options for patients with advanced melanoma have made tremendous strides in the last 2 years. At the 21st Annual Conference of the National Comprehensive Cancer Network (NCCN), in Hollywood, Florida, John A. Thompson, MD, who has joint appointments at the University of Washington School of Medicine, Fred Hutchinson Cancer Research Center, and Seattle Cancer Care Alliance, presented an update on where the field stands today.
 
“The last 5 years have witnessed a major change in the treatment of melanoma,” Thompson said. “We now have molecularly targeted agents and PD-1 agents approved by the FDA for treating melanoma.” He showed data of a trial conducted back in 1993, when options for advanced melanoma patients were quite limited. The study did not follow stage IV patients beyond 3 years, as opposed to stage I to stage III patients who were followed for over 10 years.

Role of Checkpoint Inhibitors in Melanoma

In the NCCN Guidelines version 2.2016 for melanoma, the CTLA-4 inhibitor ipilimumab has moved to second line or beyond in the metastatic or unresectable disease.
 
In ipilimumab registration trials, patients were randomized to receive ipilimumab plus a vaccine (gp100) or vaccine alone or ipilimumab alone (MDX010-20). Another trial evaluated ipilimumab with a chemotherapy agent DTIC (dacarbazine) compared with placebo and DTIC (CA184-024).  In MDX010-20, ipilimumab alone and in combination with gp100 had much better separation of the Kaplan Meier overall survival curve, compared with the vaccine alone. Additionally, the tail of the curve plateaued out, and longer term survival studies with ipilimumab as monotherapy are now ongoing, evaluating a 10-year follow-up.
 
Thompson told the audience that in evaluating patients in the clinic who are being treated with immunotherapy, it is important to remember that we sometimes have to wait till the immune response has been sufficiently activated. Disease progression is often observed before the patients respond to treatment, a phenomenon described as “pseudo-progression.” Thompson emphasized that healthcare providers need to be aware of this when treating patients with these immune checkpoint inhibitors.
 
Ipilimumab can trigger numerous immune-related AEs (irAEs), said Thompson, and physicians need to familiarize themselves with the toxicity profiles of these agents. irAEs vary from pruritis and rash to gastrointestinal symptoms like diarrhea and bowel perforation, as well as endocrine and neurological effects. He emphasized the importance of patient education on irAEs. “Early recognition of symptoms and early intervention are very important,” said Thompson. And patient advocates agree that there’s lack of information and a lot of unknowns as far as irAEs are concerned.

The data have been very promising for melanoma, Thompson told the audience, as is evident from the approval of nivolumab and pembrolizumab, both PD-1 inhibitors, in the treatment of melanoma. Studies have observed months of stable disease and a high rate of complete or partial response (CR or PR) in patients with refractory melanoma who were treated with nivolumab. Similarly, very encouraging results have been observed with pembrolizumab in ipilimumab-refractory advanced melanoma patients.



 
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