Earlier Use of Checkpoint Inhibitors in Melanoma

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The CTLA-4 inhibitor ipilimumab and the PD-1 inhibitors nivolumab and pembrolizumab are all approved as treatments for patients with metastatic melanoma. At this time, in the absence of prospective clinical trial data, selecting an immune checkpoint inhibitor to administer is a controversial area, notes Richard Joseph, MD. This is particularly true, since in clinical trials the outcomes have been similar with each of the PD-1 agents.

At this point, Joseph would consider all of these agents as appropriate therapies, with treatment individualized to each patient. So far, there are positive overall survival data for nivolumab compared with dacarbazine as first-line therapy. Additionally, results from a pooled analysis from 12 studies has demonstrated a long-term survival benefit with ipilimumab that extends beyond 10 years for some patients with advanced melanoma.¹ In this 1861-patient analysis, the median OS was 11.4 months. Interestingly, there was a plateau in the survival curve at 3 years, with a 10-year survival rate of approximately 20%.

Several other studies that have already accrued that could help answer the question of which therapy should be administered in the frontline setting, says Omid Hamid, MD. Fortunately, the FDA has already approved the PD-1 inhibitors, based on response rate and response duration. In the separate pivotal studies in varying patient populations, the ORR was 32% with nivolumab and 24% with pembrolizumab.

PD-1 inhibitors could become the first-line standard of care for patients with metastatic melanoma, suggests Howard Kaufman, MD. However, oher important questions center on sequencing of immunotherapies with other therapies, and whether this could impact long-term outcomes.

1. Schadendorf D, Hodi FS, Robert C. Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma [published online February 9, 2015]. J Clin Oncol.