TY - JOUR
T1 - Efficacy and safety outcomes in patients with advanced melanoma who discontinued treatment with nivolumab and ipilimumab because of adverse events
T2 - A pooled analysis of randomized phase II and III trials
AU - Schadendorf, Dirk
AU - Wolchok, Jedd D.
AU - Stephen Hodi, F.
AU - Chiarion-Sileni, Vanna
AU - Gonzalez, Rene
AU - Rutkowski, Piotr
AU - Grob, Jean Jacques
AU - Lance Cowey, C.
AU - Lao, Christopher D.
AU - Chesney, Jason
AU - Robert, Caroline
AU - Grossmann, Kenneth
AU - McDermott, David
AU - Walker, Dana
AU - Bhore, Rafia
AU - Larkin, James
AU - Postow, Michael A.
N1 - Publisher Copyright:
Copyright © 2017 American Society of Clinical Oncology. All rights reserved.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85034023934&partnerID=8YFLogxK
U2 - 10.1200/JCO.2017.73.2289
DO - 10.1200/JCO.2017.73.2289
M3 - Article
C2 - 28841387
AN - SCOPUS:85034023934
SN - 0732-183X
VL - 35
SP - 3807
EP - 3814
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 34
ER -