Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma.
Document Type
Article
Abstract
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.).
Medical Subject Headings
Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Carcinoma, Renal Cell; Chemotherapy, Adjuvant; Disease-Free Survival; Double-Blind Method; Female; Humans; Intention to Treat Analysis; Kidney Neoplasms; Male; Middle Aged; Nephrectomy; Recurrence; Survival Analysis
Publication Date
8-19-2021
Publication Title
The New England journal of medicine
ISSN
1533-4406
Volume
385
Issue
8
First Page
683
Last Page
694
PubMed ID
34407342
Digital Object Identifier (DOI)
10.1056/NEJMoa2106391
Recommended Citation
Choueiri, Toni K; Tomczak, Piotr; Park, Se Hoon; Venugopal, Balaji; Ferguson, Thomas; Chang, Yen-Hwa; Hajek, Jaroslav; Symeonides, Stefan N; Lee, Jae Lyun; Sarwar, Naveed; Thiery-Vuillemin, Antoine; Gross-Goupil, Marine; Mahave, Mauricio; Haas, Naomi B; Sawrycki, Piotr; Gurney, Howard; Chevreau, Christine; Melichar, Bohuslav; Kopyltsov, Evgeniy; Alva, Ajjai; Burke, John M; Doshi, Gurjyot; Topart, Delphine; Oudard, Stephane; Hammers, Hans; Kitamura, Hiroshi; Bedke, Jens; Perini, Rodolfo F; Zhang, Pingye; Imai, Kentaro; Willemann-Rogerio, Jaqueline; Quinn, David I; Powles, Thomas; and Galamaga, Rob, "Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma." (2021). ENT and Skull Base Surgery. 24.
https://scholar.barrowneuro.org/ent-and-skull-base-surgery/24