J Gynecol Oncol.  2024 Mar;35(2):e40. 10.3802/jgo.2024.35.e40.

Analysis of East Asia subgroup in Study 309/KEYNOTE-775: lenvatinib plus pembrolizumab versus treatment of physician’s choice chemotherapy in patients with previously treated advanced or recurrent endometrial cancer

• Yonemori K
• Fujiwara K
• Hasegawa K
• Yunokawa M
• Ushijima K
• Suzuki S
• Shikama A
• Minobe S
• Usami T
• Kim JW
• Kim BG
• Wang PH
• Chang TC
• Yamamoto K
• Han S
• McKenzie J
• Orlowski RJ
• Miura T
• Makker V
• Kim YM

• KMID: 2564881
• DOI: http://doi.org/10.3802/jgo.2024.35.e40

Abstract

Objective
In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician’s choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis.
Methods
Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/ adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis.
Results
Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1–43.0) months. Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49–1.10) and 0.64 (0.44–0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45–1.02) and 0.61 (0.41–0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3–5, 74% and 72%), respectively.
Conclusion
Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC.

Keyword

Asian; Chemotherapy; Endometrial Cancer; Immunotherapy; Drug Therapy; Combination; Survival