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

Authors

Kan Yonemori
Keiichi Fujiwara
Kosei Hasegawa
Mayu Yunokawa
Kimio Ushijima
Shiro Suzuki
Ayumi Shikama
Shinichiro Minobe
Tomoka Usami
Jae-Weon Kim
Byoung-Gie Kim
Peng-Hui Wang
Ting-Chang Chang
Keiko Yamamoto
Shirong Han
Jodi McKenzie
Robert J Orlowski
Takuma Miura
Vicky Makker
Yong Man Kim

Publication Date

3-1-2024

Journal

Journal of Gynecologic Oncology

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.

Keywords

Humans, Female, Neoplasm Recurrence, Local, Endometrial Neoplasms, Asia, Eastern, Physicians, Antineoplastic Combined Chemotherapy Protocols, Phenylurea Compounds, Quinolines, Antibodies, Monoclonal, Humanized

Comments

Trial Registration: ClinicalTrials.gov Identifier: NCT03517449

Supplementary Materials

PMID: 38302725