Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

Published on Sep 11, 2017in The New England Journal of Medicine74.699
· DOI :10.1056/NEJMOA1709684
Jedd D. Wolchok148
Estimated H-index: 148
(Cornell University),
Vanna Chiarion-Sileni57
Estimated H-index: 57
+ 30 AuthorsJames Larkin95
Estimated H-index: 95
(University of Duisburg-Essen)
Sources
Abstract
BackgroundNivolumab combined with ipilimumab resulted in longer progression-free survival and a higher objective response rate than ipilimumab alone in a phase 3 trial involving patients with advanced melanoma. We now report 3-year overall survival outcomes in this trial. MethodsWe randomly assigned, in a 1:1:1 ratio, patients with previously untreated advanced melanoma to receive nivolumab at a dose of 1 mg per kilogram of body weight plus ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses, followed by nivolumab at a dose of 3 mg per kilogram every 2 weeks; nivolumab at a dose of 3 mg per kilogram every 2 weeks plus placebo; or ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses plus placebo, until progression, the occurrence of unacceptable toxic effects, or withdrawal of consent. Randomization was stratified according to programmed death ligand 1 (PD-L1) status, BRAF mutation status, and metastasis stage. The two primary end points were progression-free survival a...
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#1Hussein Abdul-Hassan Tawbi (University of Texas MD Anderson Cancer Center)H-Index: 25
#2Peter A. Forsyth (USF: University of South Florida)H-Index: 29
Last. Kim Margolin (City of Hope National Medical Center)H-Index: 80
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Abstract Background Brain metastases are a common cause of disabling neurologic complications and death in patients with metastatic melanoma. Previous studies of nivolumab combined with ipilimumab ...
493 CitationsSource
#1Georgina V. Long (USYD: University of Sydney)H-Index: 107
#2Victoria Atkinson (UQ: University of Queensland)H-Index: 30
Last. Grant A. McArthur (University of Melbourne)H-Index: 91
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Summary Background Nivolumab monotherapy and combination nivolumab plus ipilimumab increase proportions of patients achieving a response and survival versus ipilimumab in patients with metastatic melanoma; however, efficacy in active brain metastases is unknown. We aimed to establish the efficacy and safety of nivolumab alone or in combination with ipilimumab in patients with active melanoma brain metastases. Methods This multicentre open-label randomised phase 2 trial was done at four sites in ...
388 CitationsSource
#1Georgina V. Long (USYD: University of Sydney)H-Index: 107
#2Keith T. Flaherty (Harvard University)H-Index: 133
Last. J.-J. GrobH-Index: 22
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Background: Previous analysis of COMBI-d (NCT01584648) demonstrated improved progression-free survival (PFS) and overall survival (OS) with combination dabrafenib and trametinib versus dabrafenib monotherapy in BRAF V600E/K-mutant metastatic melanoma. This study was continued to assess 3-year landmark efficacy and safety after >= 36-month follow-up for all living patients. Patients and methods: This double-blind, phase 3 study enrolled previously untreated patients with BRAF V600E/K-mutant unres...
307 CitationsSource
#1Caroline RobertH-Index: 127
#2Georgina V. Long (USYD: University of Sydney)H-Index: 107
Last. Antoni Ribas (UCLA: University of California, Los Angeles)H-Index: 143
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9504Background: Pembro demonstrated superior PFS and OS vs ipi in ipi-naive pts with advanced melanoma in the phase 3 KEYNOTE-006 study (NCT01866319). Here, we present long-term outcomes for all pts and in those pts who completed pembro therapy. Methods: Eligible pts (N = 834) were randomized 1:1:1 to pembro 10 mg/kg Q2W, pembro 10 mg/kg Q3W, or ipi 3 mg/kg Q3W for 4 doses. Treatment was continued for 2 yr (pembro only) or until disease progression, intolerable toxicity, or pt/investigator decis...
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#1F. Stephen Hodi (Harvard University)H-Index: 126
#2Jason Chesney (University of Louisville)H-Index: 50
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Summary Background Results from phase 2 and 3 trials in patients with advanced melanoma have shown significant improvements in the proportion of patients achieving an objective response and prolonged progression-free survival with the combination of nivolumab (an anti-PD-1 antibody) plus ipilimumab (an anti-CTLA-4 antibody) compared with ipilimumab alone. We report 2-year overall survival data from a randomised controlled trial assessing this treatment in previously untreated advanced melanoma. ...
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#1James Larkin (The Royal Marsden NHS Foundation Trust)H-Index: 95
#2Vanna Chiarion-Sileni (IEO: European Institute of Oncology)H-Index: 57
Last. Jedd D. Wolchok (Cornell University)H-Index: 148
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The median progression-free survival was 11.5 months (95% confidence interval [CI], 8.9 to 16.7) with nivolumab plus ipilimumab, as compared with 2.9 months (95% CI, 2.8 to 3.4) with ipilimumab (hazard ratio for death or disease progression, 0.42; 99.5% CI, 0.31 to 0.57; P<0.001), and 6.9 months (95% CI, 4.3 to 9.5) with nivolumab (hazard ratio for the comparison with ipilimumab, 0.57; 99.5% CI, 0.43 to 0.76; P<0.001). In patients with tumors positive for the PD-1 ligand (PD-L1), the median prog...
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#1Caroline Robert (University of Paris-Sud)H-Index: 127
#2Jacob SchachterH-Index: 46
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Background The immune checkpoint inhibitor ipilimumab is the standard-of-care treatment for patients with advanced melanoma. Pembrolizumab inhibits the programmed cell death 1 (PD-1) immune checkpoint and has antitumor activity in patients with advanced melanoma. Methods In this randomized, controlled, phase 3 study, we assigned 834 patients with advanced melanoma in a 1:1:1 ratio to receive pembrolizumab (at a dose of 10 mg per kilogram of body weight) every 2 weeks or every 3 weeks or four dos...
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#1Michael A. Postow (Cornell University)H-Index: 75
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BackgroundIn a phase 1 dose-escalation study, combined inhibition of T-cell checkpoint pathways by nivolumab and ipilimumab was associated with a high rate of objective response, including complete responses, among patients with advanced melanoma. MethodsIn this double-blind study involving 142 patients with metastatic melanoma who had not previously received treatment, we randomly assigned patients in a 2:1 ratio to receive ipilimumab (3 mg per kilogram of body weight) combined with either nivo...
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#1Dirk Schadendorf (University of Duisburg-Essen)H-Index: 137
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Purpose To provide a more precise estimate of long-term survival observed for ipilimumab-treated patients with advanced melanoma, we performed a pooled analysis of overall survival (OS) data from multiple studies. Methods The primary analysis pooled OS data for 1,861 patients from 10 prospective and two retrospective studies of ipilimumab, including two phase III trials. Patients were previously treated (n = 1,257) or treatment naive (n = 604), and the majority of patients received ipilimumab 3 ...
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A B S T R AC T Background Ipilimumab monotherapy (at a dose of 3 mg per kilogram of body weight), as compared with glycoprotein 100, improved overall survival in a phase 3 study involving patients with previously treated metastatic melanoma. We conducted a phase 3 study of ipilimumab (10 mg per kilogram) plus dacarbazine in patients with previously untreated metastatic melanoma. Methods We randomly assigned 502 patients with previously untreated metastatic melanoma, in a 1:1 ratio, to ipilimumab...
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