Lenvatinib plus pembrolizumab for advanced endometrial cancer Journal Article


Authors: Makker, V.; Colombo, N.; Casado Herráez, A.; Santin, A. D.; Colomba, E.; Miller, D. S.; Fujiwara, K.; Pignata, S.; Baron-Hay, S.; Ray-Coquard, I.; Shapira-Frommer, R.; Ushijima, K.; Sakata, J.; Yonemori, K.; Kim, Y. M.; Guerra, E. M.; Sanli, U. A.; McCormack, M. M.; Smith, A. D.; Keefe, S.; Bird, S.; Dutta, L.; Orlowski, R. J.; Lorusso, D.; for the Study 309–KEYNOTE-775 Investigators
Article Title: Lenvatinib plus pembrolizumab for advanced endometrial cancer
Abstract: BACKGROUND Standard therapy for advanced endometrial cancer after failure of platinum-based chemotherapy remains unclear. METHODS In this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced endometrial cancer who had previously received at least one platinum-based chemotherapy regimen to receive either lenvatinib (20 mg, administered orally once daily) plus pembrolizumab (200 mg, administered intravenously every 3 weeks) or chemotherapy of the treating physician’s choice (doxorubicin at 60 mg per square meter of body-surface area, administered intravenously every 3 weeks, or paclitaxel at 80 mg per square meter, administered intravenously weekly [with a cycle of 3 weeks on and 1 week off]). The two primary end points were progression-free survival as assessed on blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1, and overall survival. The end points were evaluated in patients with mismatch repair–proficient (pMMR) disease and in all patients. Safety was also assessed. RESULTS A total of 827 patients (697 with pMMR disease and 130 with mismatch repair–deficient disease) were randomly assigned to receive lenvatinib plus pembrolizumab (411 patients) or chemotherapy (416 patients). The median progression-free survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 6.6 vs. 3.8 months; hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.50 to 0.72; P<0.001; overall: 7.2 vs. 3.8 months; hazard ratio, 0.56; 95% CI, 0.47 to 0.66; P<0.001). The median overall survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 17.4 vs. 12.0 months; hazard ratio for death, 0.68; 95% CI, 0.56 to 0.84; P<0.001; overall: 18.3 vs. 11.4 months; hazard ratio, 0.62; 95% CI, 0.51 to 0.75; P<0.001). Adverse events of grade 3 or higher occurred in 88.9% of the patients who received lenvatinib plus pembrolizumab and in 72.7% of those who received chemotherapy. CONCLUSIONS Lenvatinib plus pembrolizumab led to significantly longer progression-free survival and overall survival than chemotherapy among patients with advanced endometrial cancer. (Funded by Eisai and Merck Sharp and Dohme [a subsidiary of Merck]; Study 309–KEYNOTE-775 ClinicalTrials.gov number, NCT03517449.). Copyright © 2022 Massachusetts Medical Society.
Keywords: adult; controlled study; aged; aged, 80 and over; middle aged; survival analysis; clinical trial; mortality; antineoplastic agent; endometrial neoplasms; randomized controlled trial; antineoplastic combined chemotherapy protocols; monoclonal antibody; multicenter study; phase 3 clinical trial; endometrium tumor; quinolines; quinoline derivative; antibodies, monoclonal, humanized; phenylurea compounds; very elderly; lenvatinib; carbanilamide derivative; humans; human; female; pembrolizumab
Journal Title: New England Journal of Medicine
Volume: 386
Issue: 5
ISSN: 0028-4793
Publisher: Massachusetts Medical Society  
Date Published: 2022-02-03
Start Page: 437
End Page: 448
Language: English
DOI: 10.1056/NEJMoa2108330
PUBMED: 35045221
PROVIDER: scopus
PMCID: PMC11651366
DOI/URL:
Notes: Article -- Export Date: 1 March 2022 -- Source: Scopus
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  1. Vicky Makker
    267 Makker