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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 D1, Wolchok JD1, Hodi FS1, Chiarion-Sileni V1, Gonzalez R1, Rutkowski P1, Grob JJ1, Cowey CL1, Lao CD1, Chesney J1,Robert C1, Grossmann K1, McDermott D1, Walker D1, Bhore R1, Larkin J1, Postow MA1.

Author information

1Dirk 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 Sklodowska 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 Université Paris-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 City, UT; Dana Walker and Rafia Bhore, Bristol-Myers Squibb, Princeton, NJ; and James Larkin, Royal Marsden Hospital, London, United Kingdom.

Abstract

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.

https://www.ncbi.nlm.nih.gov/pubmed/28841387