Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma

Tony K. Choueiri*, Piotr Tomczak, Se Hoon Park, Balaji Venugopal, Tom Ferguson, Stefan N Symeonides, Jaroslav Hajek, Yen Hwa Chang, Jae-Lyun Lee, Naveed Sarwar, Naomi B. Haas, Howard Gurney, Piotr Sawrycki, Mauricio Mahave, Marine Gross-Goupil, Tian Zhang, John M. Burke, Gurjyot Doshi, Bohuslav Melichar, Evgeniy KopyltsovAjjai Alva, Stephane Oudard, Delphine Topart, Hans Hammer, Hiroshi Kitamura, David F. McDermott, Adriano Silva, Eric Winquist, Jerry Cornell, Aymen Elfiky, Joseph E. Burgents, Rodolfo F. Perini, Thomas Powles

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Background
Adjuvant pembrolizumab therapy after surgery for renal-cell carcinoma was approved on the basis of a significant improvement in disease-free survival in the KEYNOTE-564 trial. Whether the results regarding overall survival from the third prespecified interim analysis of the trial would also favor pembrolizumab was uncertain.

Methods
In this phase 3, double-blind, placebo-controlled trial, we randomly assigned (in a 1:1 ratio) participants with clear-cell renal-cell carcinoma who had an increased risk of recurrence after surgery to receive pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks for up to 17 cycles (approximately 1 year) or until recurrence, the occurrence of unacceptable toxic effects, or withdrawal of consent. A significant improvement in disease-free survival according to investigator assessment (the primary end point) was shown previously. Overall survival was the key secondary end point. Safety was a secondary end point.
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Results
A total of 496 participants were assigned to receive pembrolizumab and 498 to receive placebo. As of September 15, 2023, the median follow-up was 57.2 months. The disease-free survival benefit was consistent with that in previous analyses (hazard ratio for recurrence or death, 0.72; 95% confidence interval [CI], 0.59 to 0.87). A significant improvement in overall survival was observed with pembrolizumab as compared with placebo (hazard ratio for death, 0.62; 95% CI, 0.44 to 0.87; P=0.005). The estimated overall survival at 48 months was 91.2% in the pembrolizumab group, as compared with 86.0% in the placebo group; the benefit was consistent across key subgroups. Pembrolizumab was associated with a higher incidence of serious adverse events of any cause (20.7%, vs. 11.5% with placebo) and of grade 3 or 4 adverse events related to pembrolizumab or placebo (18.6% vs. 1.2%). No deaths were attributed to pembrolizumab therapy.

Conclusions
Adjuvant pembrolizumab was associated with a significant and clinically meaningful improvement in overall survival, as compared with placebo, among participants with clear-cell renal-cell carcinoma at increased risk for recurrence after surgery. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; KEYNOTE-564 ClinicalTrials.gov number, NCT03142334.)
Original languageEnglish
JournalNew England Journal of Medicine
DOIs
Publication statusPublished - 17 Apr 2024

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