TY - JOUR
T1 - Adjuvant pembrolizumab after nephrectomy in renal-cell carcinoma
AU - Choueiri, Toni K.
AU - Tomczak, Piotr
AU - Park, Se Hoon
AU - Venugopal, Balaji
AU - Ferguson, Thomas
AU - Chang, Yen Hwa
AU - Hajek, Jaroslav
AU - Symeonides, Stefan N.
AU - Lee, Jae Lyun
AU - Sarwar, Naveed
AU - Thiery-Vuillemin, Antoine
AU - Gross-Goupil, Marine
AU - Mahave, Mauricio
AU - Haas, Naomi B.
AU - Sawrycki, Piotr
AU - Gurney, Howard
AU - Chevreau, Christine
AU - Melichar, Bohuslav
AU - Kopyltsov, Evgeniy
AU - Alva, Ajjai
AU - Burke, John M.
AU - Doshi, Gurjyot
AU - Topart, Delphine
AU - Oudard, Stephane
AU - Hammers, Hans
AU - Kitamura, Hiroshi
AU - Bedke, Jens
AU - Perini, Rodolfo F.
AU - Zhang, Pingye
AU - Imai, Kentaro
AU - Willemann-Rogerio, Jaqueline
AU - Quinn, David I.
AU - Powles, Thomas
N1 - Publisher Copyright:
© 2021 Massachussetts Medical Society. All rights reserved.
PY - 2021
Y1 - 2021
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.
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U2 - 10.1056/nejmoa2106391
DO - 10.1056/nejmoa2106391
M3 - Article
C2 - 34407342
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 -