Adjuvant pembrolizumab after nephrectomy in renal-cell carcinoma

Choueiri, T. K. et al. (2021) Adjuvant pembrolizumab after nephrectomy in renal-cell carcinoma. New England Journal of Medicine, 385(8), pp. 683-694. (doi: 10.1056/NEJMoa2106391) (PMID:34407342)

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.).

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Venugopal, Dr Balaji
• Authors: Choueiri, T. K., Tomczak, P., Park, S. H., Venugopal, B., Ferguson, T., Chang, Y.-H., Hajek, J., Symeonides, S. N., Lee, J. L., Sarwar, N., Thiery-Vuillemin, A., Gross-Goupil, M., Mahave, M., Haas, N. B., Sawrycki, P., Gurney, H., Chevreau, C., Melichar, B., Kopyltsov, E., Alva, A., Burke, J. M., Doshi, G., Topart, D., Oudard, S., Hammers, H., Kitamura, H., Bedke, J., Perini, R. F., Zhang, P., Imai, K., Willemann-Rogerio, J., Quinn, D. I., and Powles, T.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: New England Journal of Medicine
• Publisher: Massachusetts Medical Society
• ISSN: 0028-4793
• ISSN (Online): 1533-4406
• Copyright Holders: Copyright © 2021 Massachusetts Medical Society
• First Published: First published in New England Journal of Medicine 385(8):683-694
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher