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J Clin Oncol. 2017 Dec 1;35(34):3815-3822. doi: 10.1200/JCO.2016.72.1167. Epub 2017 Sep 15.

Pooled Analysis Safety Profile of Nivolumab and Ipilimumab Combination Therapy in Patients With Advanced Melanoma.

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Mario Sznol, Yale Comprehensive Cancer Center, New Haven, CT; Pier Francesco Ferrucci, Istituto Europeo di Oncologia, Milan; Massimo Guidoboni, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy; David Hogg, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Michael B. Atkins, Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC; Pascal Wolter, University Hospitals Leuven, Leuven, Belgium; Celeste Lebbé, Université Paris Diderot, Paris; Luc Thomas, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France; John M. Kirkwood, Hillman Cancer Center, Pittsburgh, PA; Jacob Schachter, Sheba Medical Center, Ramat Gan, Israel; Gregory A. Daniels, University of California San Diego, Moores Cancer Center, La Jolla, CA; Jessica Hassel, University Hospital, Heidelberg, Germany; Jonathan Cebon, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria; Winald Gerritsen, University of Queensland, St Lucia; Victoria Atkinson, Gallipoli Medical Research Foundation, Greenslopes; Victoria Atkinson, Princess Alexandra Hospital, Brisbane, Queensland, Australia; Winald Gerritsen, Radboud University Medical Center, Nijmegen, the Netherlands; John McCaffrey, Irish Clinical Oncology Research Group, Dublin; Derek Power, Irish Clinical Oncology Research Group, Cork, Ireland; Dana Walker, Rafia Bhore, and Joel Jiang, Bristol-Myers Squibb, Princeton, NJ; F. Stephen Hodi, Dana-Farber Cancer Institute, Boston, MA; and Jedd D. Wolchok, Parker Institute and Ludwig Center at Memorial Sloan Kettering Cancer Center, New York, NY.


Purpose The addition of nivolumab (anti-programmed death-1 antibody) to ipilimumab (anti-cytotoxic T-cell lymphocyte-associated 4 antibody) in patients with advanced melanoma improves antitumor response and progression-free survival but with a higher frequency of adverse events (AEs). This cross-melanoma study describes the safety profile of the approved nivolumab plus ipilimumab regimen. Methods This retrospective safety review on data from three trials (phase I, II, and III) included patients with advanced melanoma who received at least one dose of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks × 4 and then nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity while following established guidelines for AE management. Analyses were of all treatment-related AEs, select (immune-related) AEs, time to onset and resolution, and use of immune-modulating agents and their effects on outcome. Results Among 448 patients, median duration of follow-up was 13.2 months. Treatment-related grade 3/4 AEs occurred in 55.5% of patients; 35.7% had treatment-related AEs that led to discontinuation. The most frequent treatment-related select AEs of any grade were skin (64.3%) and GI (46.7%) and of grade 3/4, hepatic (17.0%) and GI (16.3%); 30.1% developed a grade 2 to 4 select AE in more than one organ category. Median time to onset of grade 3/4 treatment-related select AEs ranged from 3.1 (skin) to 16.3 (renal) weeks, and with the exclusion of endocrine AEs, median time to resolution from onset ranged from 1.9 (renal) to 4.5 (pulmonary) weeks, with resolution rates between 79% and 100% while using immune-modulating agents. Four (< 1%) on-study deaths were attributed to therapy. Conclusion Frequency of grade 3/4 treatment-related AEs was higher with nivolumab plus ipilimumab and occurred earlier than historical experience with either agent alone, but resolution rates were similar.

[Indexed for MEDLINE]

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