KEY TAKEAWAYS
- The phase III KEYNOTE-775 trial (NCT03517449) evaluated the efficacy and safety of Lenvatinib plus Pembrolizumab in 827 patients with advanced, recurrent, or metastatic EC.
- The primary aim was to evaluate the efficacy of the combination of Lenvatinib plus Pembrolizumab versus chemotherapy based on the physician’s choice regarding OS, PFS, and ORR.
- The method randomly assigned patients to two groups, with one group receiving Lenvatinib plus Pembrolizumab and the other receiving chemotherapy.
- The combination of Lenvatinib plus Pembrolizumab demonstrated significant improvements in OS, PFS, and ORR compared to chemotherapy.
- The HR for OS and PFS was lower in patients with pMMR tumors than in all-comers.
- Lenvatinib plus Pembrolizumab demonstrated sustained efficacy and tolerable safety in individuals with advanced EC who had received prior treatment compared to chemotherapy. No newly identified safety concerns were noted.
The conclusive prespecified evaluation for overall survival (OS), in addition to the latest progression-free survival (PFS) and objective response rate (ORR), and safety data are presented from the open-label, randomized, phase III Study 309/KEYNOTE-775. A cohort of 827 patients diagnosed with advanced, recurrent, or metastatic endometrial cancer (EC) were subjected to a random assignment. The patients were divided into two groups, with one group receiving lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously once every 3 weeks (n = 411), while the other group received chemotherapy based on the physician’s choice (doxorubicin 60 mg/m2 intravenously once every 3 weeks or paclitaxel 80 mg/m2 intravenously once weekly [3 weeks on; 1 week off] [n = 416]).
The efficacy of the treatment was reported for patients with proficient mismatch repair (pMMR) tumors and for all patients, including various subgroups based on factors such as histology, prior therapy, and MMR status. There were reports of improved safety. The combination of Lenvatinib and Pembrolizumab has demonstrated significant improvements in Overall Survival (OS) and Progression-Free Survival (PFS), as well as Objective Response Rate (ORR) when compared to chemotherapy. The pMMR Hazard Ratio (HR) for OS was 0.70 with a 95% Confidence Interval (CI) of 0.58 to 0.83, while the all-comer HR was 0.65 with a 95% CI of 0.55 to 0.77. The pMMR HR for PFS was 0.60 with a 95% CI of 0.50 to 0.72, and the all-comer HR was 0.56 with a 95% CI of 0.48 to 0.66. The ORR for pMMR patients was 32.4% compared to 15.1% for chemotherapy; for all-comers, the ORR was 33.8% compared to 14.7% for chemotherapy. Lenvatinib, in combination with pembrolizumab, demonstrated favorable outcomes in terms of OS (overall survival), PFS (progression-free survival), and ORR (objective response rate) across all subgroups of interest. There were no newly identified safety concerns noted. The combination of Lenvatinib and Pembrolizumab demonstrated sustained efficacy and tolerable safety in individuals with advanced EC who had received prior treatment compared to chemotherapy.
Source: https://pubmed.ncbi.nlm.nih.gov/37058687/
Clinical Trail: https://clinicaltrials.gov/ct2/show/NCT03517449
Makker V, Colombo N, Herráez AC, Monk BJ, Mackay H, Santin AD, Miller DS, Moore RG, Baron-Hay S, Ray-Coquard I, Ushijima K, Yonemori K, Kim YM, Guerra Alia EM, Sanli UA, Bird S, Orlowski R, McKenzie J, Okpara C, Barresi G, Lorusso D. Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775. J Clin Oncol. 2023 Apr 14:JCO2202152. doi: 10.1200/JCO.22.02152. Epub ahead of print. PMID: 37058687.
