Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma

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

AU - KEYNOTE-564 Investigators

N1 - Copyright © 2021 Massachusetts Medical Society.

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.).

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antibodies, Monoclonal, Humanized/adverse effects

KW - Antineoplastic Agents, Immunological/adverse effects

KW - Carcinoma, Renal Cell/drug therapy

KW - Chemotherapy, Adjuvant/adverse effects

KW - Disease-Free Survival

KW - Double-Blind Method

KW - Female

KW - Humans

KW - Intention to Treat Analysis

KW - Kidney Neoplasms/drug therapy

KW - Male

KW - Middle Aged

KW - Nephrectomy

KW - Recurrence

KW - Survival Analysis

U2 - 10.1056/NEJMoa2106391

DO - 10.1056/NEJMoa2106391

M3 - SCORING: Journal article

C2 - 34407342

VL - 385

SP - 683

EP - 694

JO - NEW ENGL J MED

JF - NEW ENGL J MED

SN - 0028-4793

IS - 8

ER -