• Ann Pharmacother · Aug 2015

    Review

    Current status and future directions of the immune checkpoint inhibitors ipilimumab, pembrolizumab, and nivolumab in oncology.

    • Meagan S Barbee, Adebayo Ogunniyi, Troy Z Horvat, and Thu-Oanh Dang.
    • Memorial Sloan Kettering Cancer Center, New York, NY, USA.
    • Ann Pharmacother. 2015 Aug 1; 49 (8): 907-37.

    ObjectiveTo provide the clinician with an update and the current status and future direction of approved immune checkpoint inhibitors (ICIs) in oncology.Data SourcesA PubMed search from January 1, 1966 to March 13, 2015 was performed using the key terms ipilimumab, pembrolizumab, lambrolizumab, nivolumab, immune checkpoint inhibitor, MDX-010, MDX-101, BMS-734016, MK-3475, SCH 900475, MDX-1106, BMS-936558, ONO-4538, CTLA-4, PD-1, or PD-L1 and cancer, oncology, or neoplasm. Additional references were identified from the investigators(') personal files, recent oncology meetings, review articles, clinical guidelines, and package inserts.Study Selection And Data ExtractionAll English-language clinical trials assessing the safety and efficacy of ipilimumab, nivolumab, and pembrolizumab in cancer were considered. The PubMed search resulted in 215 trials; 33 met inclusion criteria. A further 28 trials were identified from the above sources; 61 trials from 2005 to 2015 were included. We consolidated and clarified treatment recommendations for the management of immune-related adverse events (irAEs), assessed response criteria, and calculated the clinical utility of leading tumor profiling options.Data SynthesisIpilimumab and nivolumab, but not pembrolizumab, have an overall survival (OS) advantage over chemotherapy first line in unresectable/metastatic melanoma. Nivolumab has an OS advantage versus chemotherapy in second-line squamous non-small-cell lung cancer. Data in other settings are promising. Nivolumab and pembrolizumab are better tolerated than ipilimumab. Further validation of response criteria is needed. Tumor profiling to predict clinical benefit is premature but promising.ConclusionsThe treatment landscape in oncology is quickly evolving with the advent of ICIs.© The Author(s) 2015.

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