As reported in the Journal of Clinical Oncology by Vicky Makker, MD, and colleagues, an updated analysis of the phase III Study 309/KEYNOTE-775 trial showed overall and progression-free survival benefits with lenvatinib/pembrolizumab vs physician’s choice of chemotherapy among previously treated patients with advanced endometrial cancer. This benefit was seen in patients with mismatch repair–proficient (pMMR) disease as well as among all patients.
The primary analysis of the trial supported the July 2021 approval of lenvatinib plus pembrolizumab for patients with advanced endometrial carcinoma that is pMMR or not microsatellite instability–high who have disease progression after systemic therapy in any setting and are not candidates for curative surgery or radiation.
Vicky Makker, MD
Study Details
In the international open-label trial, 827 patients with advanced, recurrent, or metastatic disease were randomly assigned to receive lenvatinib at 20 mg once daily plus pembrolizumab at 200 mg once every 3 weeks (n = 411) or chemotherapy of physician’s choice (n = 416), consisting of doxorubicin at 60 mg/m2 once every 3 weeks or paclitaxel at 80 mg/m2 once weekly for 3 weeks on/1 week off. A total of 346 patients in the lenvatinib/pembrolizumab group and 351 in the chemotherapy group had pMMR disease. The updated analysis included the final prespecified analysis for overall survival.
Key Findings
As of data cutoff (in March 2022, > 16 months of additional follow-up from the primary analysis), median follow-up was 18.7 months in the lenvatinib/pembrolizumab group and 12.2 months in the chemotherapy group.
In the pMMR population, median overall survival was 18.0 months (95% confidence interval [CI] = 14.9–20.5 months) in the lenvatinib/pembrolizumab group vs 12.2 months (95% CI = 11.0–14.1 months) in the chemotherapy group (hazard ratio [HR] = 0.70, 95% CI = 0.58–0.83). In the total population, median overall survival was 18.7 months (95% CI = 15.6–21.3 months) in the lenvatinib/pembrolizumab group vs 11.9 months (95% CI = 10.7–13.3 months) in the chemotherapy group (HR = 0.65, 95% CI = 0.55–0.77).
In the pMMR population, median progression-free survival was 6.7 months (95% CI = 5.6–7.4 months) in the lenvatinib/pembrolizumab group vs 3.8 months (95% CI = 3.6–5.0 months) in the chemotherapy group (HR = 0.60, 95% CI = 0.50–0.72). In the total population, median progression-free survival was 7.3 months (95% CI = 5.7–7.6 months) in the lenvatinib/pembrolizumab group vs 3.8 months (95% CI = 3.6–4.2 months) in the chemotherapy group (HR = 0.56, 95% CI = 0.48–0.66).
In the pMMR population, objective response was observed in 32.4% vs 15.1% of patients, with median response durations of 9.3 vs 5.7 months. In the total population, objective response was observed in 33.8% v 14.7%, with median response durations of 12.9 vs 5.7 months.
Overall survival, progression-free survival, and objective response rate favored lenvatinib/pembrolizumab in all subgroups of interest. No new safety signals were observed during extended follow-up.
The investigators concluded, “Lenvatinib plus pembrolizumab continued to show improved efficacy vs chemotherapy and manageable safety in patients with previously treated advanced endometrial cancer.”
Dr. Makker, of Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Eisai Inc and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc. For full disclosures of the study authors, visit asco.org.
