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 Journal Article


Authors: Schadendorf, D.; Wolchok, J. D.; Hodi, F. S.; Chiarion-Sileni, V.; Gonzalez, R.; Rutkowski, P.; Grob, J. J.; Cowey, C. L.; Lao, C. D.; Chesney, J.; Robert, C.; Grossmann, K.; McDermott, D.; Walker, D.; Bhore, R.; Larkin, J.; Postow, M. A.
Article Title: 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
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. Copyright © 2017 American Society of Clinical Oncology. All rights reserved.
Keywords: cancer survival; controlled study; treatment outcome; disease-free survival; survival analysis; retrospective studies; major clinical study; overall survival; mortality; hepatitis; advanced cancer; cancer combination chemotherapy; diarrhea; dose response; drug efficacy; drug safety; drug withdrawal; monotherapy; side effect; systemic therapy; disease free survival; cancer staging; follow up; neoplasm staging; ipilimumab; cancer immunotherapy; melanoma; progression free survival; liver toxicity; skin neoplasms; kidney disease; proportional hazards models; drug administration schedule; randomized controlled trials as topic; pathology; dose-response relationship, drug; retrospective study; monoclonal antibody; alanine aminotransferase blood level; aspartate aminotransferase blood level; pneumonia; alanine aminotransferase; aspartate aminotransferase; cause of death; skin tumor; antibodies, monoclonal; proportional hazards model; drug therapy, combination; clinical trials, phase iii as topic; pneumothorax; patient safety; colitis; skin disease; neoplasm invasiveness; kaplan meier method; hypothyroidism; drug administration; connective tissue disease; corticosteroid; autoimmune disease; clinical trials, phase ii as topic; triacylglycerol lipase blood level; factual database; databases, factual; urogenital tract disease; neurologic disease; metabolic disorder; adverse drug reaction; heart ventricle arrhythmia; statistics, nonparametric; treatment withdrawal; musculoskeletal disease; induction chemotherapy; triacylglycerol lipase; iatrogenic disease; randomized controlled trial (topic); phase 2 clinical trial (topic); phase 3 clinical trial (topic); kaplan-meier estimate; hypopituitarism; nonparametric test; clinical outcome; corticosteroid therapy; tumor invasion; withholding treatment; maintenance chemotherapy; combination drug therapy; mediastinum disease; nutritional disorder; adrenal cortex insufficiency; nivolumab; humans; prognosis; human; male; female; priority journal; article; evaluation study; statistics and numerical data
Journal Title: Journal of Clinical Oncology
Volume: 35
Issue: 34
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2017-12-01
Start Page: 3807
End Page: 3814
Language: English
DOI: 10.1200/jco.2017.73.2289
PUBMED: 28841387
PROVIDER: scopus
PMCID: PMC5791828
DOI/URL:
Notes: Article -- Export Date: 2 January 2018 -- Source: Scopus
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MSK Authors
  1. Jedd D Wolchok
    656 Wolchok
  2. Michael Andrew Postow
    185 Postow