Long-term results encouraging for combination immunotherapy for advanced melanoma

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Sznol, clinical research leader of the melanoma research program at Yale Cancer Center, was the senior author on the original study of combination immunotherapy that was first published in the New England Journal of Medicine and presented at ASCO in 2013. Dr Jedd Wolchok of Memorial Sloan Kettering Cancer Center was first author of the earlier study, and senior author of this updated research.

The trial evaluated the safety and activity of the combination regimen of nivolumab (anti-PD-1), an investigational PD-1 immune checkpoint inhibitor, and ipilimumab (anti-CTLA-4; Yervoy), given either concurrently or sequentially, to patients with advanced melanoma whose disease progressed after prior treatment. The one-year overall survival rate was 94% and the two-year rate was 88%.

"The treatment of advanced melanoma has changed dramatically in the last few years, but there continues to be a need to increase the number of patients who experience a long-term survival benefit," Sznol said. "While these are phase 1b data, the duration of response and one- and two-year survival rates observed with the combination regimen of nivolumab and Yervoy are very encouraging and support the rationale for the ongoing, late-stage trials of this combination regimen."

CTLA-4 and PD-1 are targets for cancer immunotherapy because they are shut down the immune system's ability to respond to attack tumors. Antibodies blocking CTLA-4 and PD-1 enable a strong immune response against cancer by removing the brakes from the immune system. Nivolumab targets the PD-1 receptor on the surface of T-cells, and ipilimumab targets CTLA-4 receptors. Both are manufactured by Bristol-Myers Squibb, which sponsored the study with Ono Pharmaceutical Company, Ltd.

Other authors are Dr Harriet Kluger, Kathleen Reed, Matthew Burke, and Anne Caldwell of Yale School of Medicine and Yale Cancer Center; Dr Margaret Callahan, Dr Michael Postow, Dr Naiyer Rizvi, Dr Alexander Lesokhin, Dr Neil Segal, Dr Charlotte Ariyan, Ruth-Ann Gordon, Stephanie Kronenberg, and Blessing Agunwamba of Memorial Sloan-Kettering Cancer Center; Xiaoling Zhang of Dako North America; and Dr Israel Lowy, Dr Hector David Inzunza, William Feely, Christine Horak, Quan Hong, Alan Korman, Dr John Wiggington, and Dr Ashok Gupta, of Bristol-Myers Squibb.

Michael Atkins of Georgetown-Lombardi Comprehensive Cancer Center and John Kirkwood University of Pittsburgh Medical Center contributed to the accrual of 41 new patients.

Source: Yale University