TY - JOUR
T1 - Adjuvant pembrolizumab after nephrectomy in renal-cell carcinoma
AU - Choueiri, T. K.
AU - Tomczak, P.
AU - Park, S. H.
AU - Venugopal, B.
AU - Ferguson, T.
AU - Chang, Y. H.
AU - Hajek, J.
AU - Symeonides, S. N.
AU - Lee, J. L.
AU - Sarwar, N.
AU - Thiery-Vuillemin, A.
AU - Gross-Goupil, M.
AU - Mahave, M.
AU - Haas, N. B.
AU - Sawrycki, P.
AU - Gurney, H.
AU - Chevreau, C.
AU - Melichar, B.
AU - Kopyltsov, E.
AU - Alva, A.
AU - Burke, J. M.
AU - Doshi, G.
AU - Topart, D.
AU - Oudard, S.
AU - Hammers, H.
AU - Kitamura, H.
AU - Bedke, J.
AU - Perini, R. F.
AU - Zhang, P.
AU - Imai, K.
AU - Willemann-Rogerio, J.
AU - Quinn, D. I.
AU - Powles, T.
AU - KEYNOTE-564 Investigators
PY - 2021/8/19
Y1 - 2021/8/19
N2 - BACKGROUND Patients with renal-cell carcinoma who undergo nephrectomy have no options for adjuvant therapy to reduce the risk of recurrence that have high levels of supporting evidence. METHODS In a double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with clear-cell renal-cell carcinoma who were at high risk for recurrence after nephrectomy, with or without metastasectomy, to receive either adjuvant pembrolizumab (at a dose of 200 mg) or placebo intravenously once every 3 weeks for up to 17 cycles (approximately 1 year).The primary end point was disease-free survival according to the investigator's assessment. Overall survival was a key secondary end point. Safety was a secondary end point. RESULTS A total of 496 patients were randomly assigned to receive pembrolizumab, and 498 to receive placebo. At the prespecified interim analysis, the median time from randomization to the data-cutoff date was 24.1 months. Pembrolizumab therapy was associated with significantly longer disease-free survival than placebo (disease- free survival at 24 months, 77.3% vs.68.1%; hazard ratio for recurrence or death, 0.68; 95% confidence interval [CI], 0.53 to 0.87; P = 0.002 [two-sided]).The estimated percentage of patients who remained alive at 24 months was 96.6% in the pembrolizumab group and 93.5% in the placebo group (hazard ratio for death, 0.54; 95% CI, 0.30 to 0.96).Grade 3 or higher adverse events of any cause occurred in 32.4% of the patients who received pembrolizumab and in 17.7% of those who received placebo. No deaths related to pembrolizumab therapy occurred. CONCLUSIONS Pembrolizumab treatment led to a significant improvement in disease-free survival as compared with placebo after surgery among patients with kidney cancer who were at high risk for recurrence.(Funded by Merck Sharp and Dohme, a subsidiary of Merck; KEYNOTE-564 ClinicalTrials.gov number, NCT03142334.
AB - BACKGROUND Patients with renal-cell carcinoma who undergo nephrectomy have no options for adjuvant therapy to reduce the risk of recurrence that have high levels of supporting evidence. METHODS In a double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with clear-cell renal-cell carcinoma who were at high risk for recurrence after nephrectomy, with or without metastasectomy, to receive either adjuvant pembrolizumab (at a dose of 200 mg) or placebo intravenously once every 3 weeks for up to 17 cycles (approximately 1 year).The primary end point was disease-free survival according to the investigator's assessment. Overall survival was a key secondary end point. Safety was a secondary end point. RESULTS A total of 496 patients were randomly assigned to receive pembrolizumab, and 498 to receive placebo. At the prespecified interim analysis, the median time from randomization to the data-cutoff date was 24.1 months. Pembrolizumab therapy was associated with significantly longer disease-free survival than placebo (disease- free survival at 24 months, 77.3% vs.68.1%; hazard ratio for recurrence or death, 0.68; 95% confidence interval [CI], 0.53 to 0.87; P = 0.002 [two-sided]).The estimated percentage of patients who remained alive at 24 months was 96.6% in the pembrolizumab group and 93.5% in the placebo group (hazard ratio for death, 0.54; 95% CI, 0.30 to 0.96).Grade 3 or higher adverse events of any cause occurred in 32.4% of the patients who received pembrolizumab and in 17.7% of those who received placebo. No deaths related to pembrolizumab therapy occurred. CONCLUSIONS Pembrolizumab treatment led to a significant improvement in disease-free survival as compared with placebo after surgery among patients with kidney cancer who were at high risk for recurrence.(Funded by Merck Sharp and Dohme, a subsidiary of Merck; KEYNOTE-564 ClinicalTrials.gov number, NCT03142334.
UR - http://www.scopus.com/inward/record.url?scp=85113283089&partnerID=8YFLogxK
U2 - 10.1056/nejmoa2106391
DO - 10.1056/nejmoa2106391
M3 - Article
AN - SCOPUS:85113283089
SN - 0028-4793
VL - 385
SP - 683
EP - 694
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 8
ER -