Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

Abstract

BACKGROUND Nivolumab 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. METHODS We 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 and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group versus the ipilimumab group. RESULTS At a minimum follow-up of 36 months, the median overall survival had not been reached in the nivolumab-plus-ipilimumab group and was 37.6 months in the nivolumab group, as compared with 19.9 months in the ipilimumab group (hazard ratio for death with nivolumab plus ipilimumab vs. ipilimumab, 0.55 [P<0.001]; hazard ratio for death with nivolumab vs. ipilimumab, 0.65 [P<0.001]). The overall survival rate at 3 years was 58% in the nivolumab-plus-ipilimumab group and 52% in the nivolumab group, as compared with 34% in the ipilimumab group. The safety profile was unchanged from the initial report. Treatment-related adverse events of grade 3 or 4 occurred in 59% of the patients in the nivolumab-plus-ipilimumab group, in 21% of those in the nivolumab group, and in 28% of those in the ipilimumab group. CONCLUSIONS Among patients with advanced melanoma, significantly longer overall survival occurred with combination therapy with nivolumab plus ipilimumab or with nivolumab alone than with ipilimumab alone. (Funded by Bristol-Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505.)

Exploring the Most Visible German Websites on Melanoma Immunotherapy: A Web-Based Analysis

“…Firstly, the websites were grouped according to their providers: (1) commercial and pharmaceutical companies, (2) non-commercial/charity providers, (3) medical or scientific providers, (4) general public press, (5) commercial health information services, (6) clinics or health professionals, and (7) Wikipedia.org. The categorization was conducted independently by two researchers (JB, TS); disagreements were discussed and remedied in a subsequent meeting.…”

“…Approvals of new effective therapies in the last decade have substantially expanded the treatment spectrum, especially for melanoma patients with metastatic disease. One of these treatment options is immunotherapy, whose application has resulted in pioneering response rates and significantly increased survival chances of melanoma patients [4][5][6].…”

Immunotherapy induced pyrexia and the role of PET/CT

“…The overall survival rate at 3 years was 58% in the combination group, 52% in the nivolumab group and 34% in the ipilumimab group (4). Treatment-related adverse effects were significantly higher with combination therapy, with grade 3/4 adverse events occurring in 59% of patients in the combination group, 21% on single agent nivolumab and 28% on ipilumimab alone (4). As a result of this trial a number of patients are now being commenced on combination immunotherapy in the first line setting.…”

Malignant Mesothelioma Clinical Trial Combines Immunotherapy Drugs

“…To put these results into perspective, it will help to consider the results from a Phase III study of ipilimumab plus nivolumab as compared with nivolumab alone for melanoma [12]. That pivotal study reported 58% objective response rate with the combined immunotherapy, compared with 44% with single-agent nivolumab.…”