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

J Clin Oncol. 2017 Dec 1;35(34):3807-3814. doi: 10.1200/JCO.2017.73.2289. Epub 2017 Aug 25.

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.

Publication types

  • Evaluation Study

MeSH terms

  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects*
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Databases, Factual
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Humans
  • Ipilimumab / administration & dosage
  • Ipilimumab / adverse effects*
  • Kaplan-Meier Estimate
  • Male
  • Melanoma / drug therapy*
  • Melanoma / mortality*
  • Melanoma / pathology
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Nivolumab
  • Patient Safety / statistics & numerical data
  • Prognosis
  • Proportional Hazards Models
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / mortality*
  • Skin Neoplasms / pathology
  • Statistics, Nonparametric
  • Survival Analysis
  • Treatment Outcome
  • Withholding Treatment

Substances

  • Antibodies, Monoclonal
  • Ipilimumab
  • Nivolumab