Medline ® Abstract for Reference 18
of 'Toxicities associated with checkpoint inhibitor immunotherapy'
Efficacy and Safety Outcomes in Patients With Advanced Melanoma Who Discontinued Treatment With Nivolumab and Ipilimumab Because of Adverse Events: A Pooled Analysis of Randomized Phase II and III Trials.
Schadendorf D, Wolchok JD, Hodi FS, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob JJ, Cowey CL, Lao CD, Chesney J, Robert C, Grossmann K, McDermott D, Walker D, Bhore R, Larkin J, Postow MA
J Clin Oncol. 2017;
Purpose Approximately 40% of patients with advanced melanoma who received nivolumab combined with ipilimumab in clinical trials discontinued treatment because of adverse events (AEs). We conducted a retrospective analysis to assess the efficacy and safety of nivolumab plus ipilimumab in patients who discontinued treatment because of AEs. Methods Data were pooled from phase II and III trials of patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, every 3 weeks for four doses, followed by nivolumab monotherapy 3 mg/kg every 2 weeks (N = 409). Efficacy was assessed in all randomly assigned patients who discontinued because of AEs during the induction phase (n = 96) and in those who did not discontinue because of AEs (n = 233). Safety was assessed in treated patients who discontinued because of AEs (n = 176) at any time and in those who did not discontinue because of AEs (n = 231). Results At a minimum follow-up of 18 months, median progression-free survival was 8.4 months for patients who discontinued treatment because of AEs during the induction phase and 10.8 months for patients who did not discontinue because of AEs ( P = .97). Median overall survival had not been reached in either group ( P = .23). The objective response rate was 58.3% for patients who discontinued because of AEs during the induction phase and 50.2% for patients who did not discontinue. The vast majority of grade 3 or 4 AEs occurred during the induction phase, with most resolving after appropriate management. Conclusion Efficacy outcomes seemed similar between patients who discontinued nivolumab plus ipilimumab treatment because of AEs during the induction phase and those who did not discontinue because of AEs. Therefore, even after discontinuation, many patients may continue to derive benefit from combination therapy.
Dirk Schadendorf, University Hospital Essen and the German Cancer Consortium, Essen, Germany; Jedd D. Wolchok and Michael A. Postow, Memorial Sloan Kettering Cancer Center; Michael A. Postow, Weill Cornell Medical College, New York, NY; F. Stephen Hodi, Dana-Farber Cancer Institute; David McDermott, Beth Israel Deaconess Medical Center, Boston, MA; Vanna Chiarion-Sileni, Istituto Oncologico Veneto, Veneto, Italy; Rene Gonzalez, University of Colorado Denver, Aurora, CO; Piotr Rutkowski, Maria Skłodowska Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland; Jean-Jacques Grob, Aix-Marseille Université, Assistance Publique Hôpitaux de Marseille Timone, Marseille; Caroline Robert, Gustave Roussy and UniversitéParis-Sud, Paris, France; C. Lance Cowey, Texas Oncology-Baylor Cancer Center, Dallas, TX; Christopher D. Lao, University of Michigan, Ann Arbor, MI; Jason Chesney, University of Louisville, Louisville, KY; Kenneth Grossmann, Huntsman Cancer Institute, Salt Lake Cit