TY - JOUR
T1 - Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma
AU - Weber, Jeffrey
AU - Mandala, Mario
AU - Del Vecchio, Michele
AU - Gogas, Helen J.
AU - Arance, Ana M.
AU - Cowey, C. Lance
AU - Dalle, Stéphane
AU - Schenker, Michael
AU - Chiarion-Sileni, Vanna
AU - Marquez-Rodas, Ivan
AU - Grob, Jean Jacques
AU - Butler, Marcus O.
AU - Middleton, Mark R.
AU - Maio, Michele
AU - Atkinson, Victoria
AU - Queirolo, Paola
AU - Gonzalez, Rene
AU - Kudchadkar, Ragini R.
AU - Smylie, Michael
AU - Meyer, Nicolas
AU - Mortier, Laurent
AU - Atkins, Michael B.
AU - Long, Georgina V.
AU - Bhatia, Shailender
AU - Lebbé, Celeste
AU - Rutkowski, Piotr
AU - Yokota, Kenji
AU - Yamazaki, Naoya
AU - Kim, Tae M.
AU - De Pril, Veerle
AU - Sabater, Javier
AU - Qureshi, Anila
AU - Larkin, James
AU - Ascierto, Paolo A.
AU - for the CheckMate 238 Collaborators
PY - 2017/11/9
Y1 - 2017/11/9
N2 - BACKGROUND: Nivolumab and ipilimumab are immune checkpoint inhibitors that have been approved for the treatment of advanced melanoma. In the United States, ipilimumab has also been approved as adjuvant therapy for melanoma on the basis of recurrence- free and overall survival rates that were higher than those with placebo in a phase 3 trial. We wanted to determine the efficacy of nivolumab versus ipilimumab for adjuvant therapy in patients with resected advanced melanoma. METHODS: In this randomized, double-blind, phase 3 trial, we randomly assigned 906 patients (≥15 years of age) who were undergoing complete resection of stage IIIB, IIIC, or IV melanoma to receive an intravenous infusion of either nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks (453 patients) or ipilimumab at a dose of 10 mg per kilogram every 3 weeks for four doses and then every 12 weeks (453 patients). The patients were treated for a period of up to 1 year or until disease recurrence, a report of unacceptable toxic effects, or withdrawal of consent. The primary end point was recurrence-free survival in the intention-totreat population. RESULTS: At a minimum follow-up of 18 months, the 12-month rate of recurrence-free survival was 70.5% (95% confidence interval [CI], 66.1 to 74.5) in the nivolumab group and 60.8% (95% CI, 56.0 to 65.2) in the ipilimumab group (hazard ratio for disease recurrence or death, 0.65; 97.56% CI, 0.51 to 0.83; P<0.001). Treatmentrelated grade 3 or 4 adverse events were reported in 14.4% of the patients in the nivolumab group and in 45.9% of those in the ipilimumab group; treatment was discontinued because of any adverse event in 9.7% and 42.6% of the patients, respectively. Two deaths (0.4%) related to toxic effects were reported in the ipilimumab group more than 100 days after treatment. CONCLUSIONS: Among patients undergoing resection of stage IIIB, IIIC, or IV melanoma, adjuvant therapy with nivolumab resulted in significantly longer recurrence-free survival and a lower rate of grade 3 or 4 adverse events than adjuvant therapy with ipilimumab.
AB - BACKGROUND: Nivolumab and ipilimumab are immune checkpoint inhibitors that have been approved for the treatment of advanced melanoma. In the United States, ipilimumab has also been approved as adjuvant therapy for melanoma on the basis of recurrence- free and overall survival rates that were higher than those with placebo in a phase 3 trial. We wanted to determine the efficacy of nivolumab versus ipilimumab for adjuvant therapy in patients with resected advanced melanoma. METHODS: In this randomized, double-blind, phase 3 trial, we randomly assigned 906 patients (≥15 years of age) who were undergoing complete resection of stage IIIB, IIIC, or IV melanoma to receive an intravenous infusion of either nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks (453 patients) or ipilimumab at a dose of 10 mg per kilogram every 3 weeks for four doses and then every 12 weeks (453 patients). The patients were treated for a period of up to 1 year or until disease recurrence, a report of unacceptable toxic effects, or withdrawal of consent. The primary end point was recurrence-free survival in the intention-totreat population. RESULTS: At a minimum follow-up of 18 months, the 12-month rate of recurrence-free survival was 70.5% (95% confidence interval [CI], 66.1 to 74.5) in the nivolumab group and 60.8% (95% CI, 56.0 to 65.2) in the ipilimumab group (hazard ratio for disease recurrence or death, 0.65; 97.56% CI, 0.51 to 0.83; P<0.001). Treatmentrelated grade 3 or 4 adverse events were reported in 14.4% of the patients in the nivolumab group and in 45.9% of those in the ipilimumab group; treatment was discontinued because of any adverse event in 9.7% and 42.6% of the patients, respectively. Two deaths (0.4%) related to toxic effects were reported in the ipilimumab group more than 100 days after treatment. CONCLUSIONS: Among patients undergoing resection of stage IIIB, IIIC, or IV melanoma, adjuvant therapy with nivolumab resulted in significantly longer recurrence-free survival and a lower rate of grade 3 or 4 adverse events than adjuvant therapy with ipilimumab.
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U2 - 10.1056/NEJMoa1709030
DO - 10.1056/NEJMoa1709030
M3 - Article
AN - SCOPUS:85033400433
VL - 377
SP - 1824
EP - 1835
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
IS - 19
ER -