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Metastatic Melanoma Cells

PD-1 Blockade Shows Promise for Patients with Metastatic Melanoma

Melanoma is the deadliest form of skin cancer. The 5-year survival rate for melanoma is 17% in cases where cancer has metastasized. Immune-based cancer treatments are changing the landscape of melanoma treatment and showing great promise for prolonging patient survival. So-called checkpoint inhibitor treatments, work by targeting molecules that serve as checks and balances in the regulation of immune responses. The programmed death 1 (PD-1) pathway limits immune responses against cancer.  Blocking the pathway with a monoclonal antibody would unleash or enhance pre-existing anti-cancer immune responses.

A recent study of pembrolizumab (Keytruda), made by Merck, examined the effects of this PD-1 blockade in patients with advanced melanoma. In an earlier study, pembrolizumab had fewer toxicities and significantly improved overall survival compared with ipilimumab, a different checkpoint inhibitor. In this study, published in JAMA, the authors sought to characterize the association of pembrolizumab with tumor response and overall survival among patients with advanced melanoma.

The results of the study were promising. In this population of 655 patients, pembrolizumab treatment was associated with an objective response rate of 33%, 12-month progression-free survival rate of 35%, a 23-month median overall survival, and a grade 3 or 4 adverse event rate of 14%, regardless of any previous ipilimumab treatment or pembrolizumab dose or schedule. Approximately 50% of all patients were alive at the 24-month time point, noteworthy considering that the median overall survival in most previous clinical trials involving patients with metastatic melanoma was consistently less than 12 months.  In addition, the safety profile observed in this analysis showed that over a 15-month follow-up, no deaths from treatment-related adverse events were reported, and only 4% of patients discontinued pembrolizumab because of a treatment-related adverse event. The authors note that the results in this study were similar to those reported for nivolumab, another PD-1 blockade approved for advanced melanoma patients.

In the accompanying editorial in JAMA, the editors note that when paired with the favorable toxicity profile of PD-1 blockade, these efficacy data highlight the benefit of this treatment approach for addressing the 2 primary goals of treatment in patients with metastatic melanoma—to prolong survival and to preserve and improve quality of life (QoL).

Byline: Martha L. Sikes, MS, RPh, PA-C

Posted: May 23, 2016

Source: Journal of the American Medical Institute (JAMA)
Adapted from the original article.

[Image: Wikimedia Commons / National Cancer Institute]

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