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

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

doi: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

J Gynecol Oncol. 2024 Mar;35(2):e40. doi: 10.3802/jgo.2024.35.e40. Epub 2024 Jan 19.

Authors

Kan Yonemori¹, Keiichi Fujiwara², Kosei Hasegawa², Mayu Yunokawa³, Kimio Ushijima⁴, Shiro Suzuki⁵, Ayumi Shikama⁶, Shinichiro Minobe⁷, Tomoka Usami⁸, Jae-Weon Kim⁹, Byoung-Gie Kim¹⁰, Peng-Hui Wang¹¹, Ting-Chang Chang¹², Keiko Yamamoto¹³, Shirong Han¹⁴, Jodi McKenzie¹⁵, Robert J Orlowski¹⁶, Takuma Miura¹⁷, Vicky Makker¹⁸, Yong Man Kim¹⁹

Affiliations

¹ Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan. kyonemor@ncc.go.jp.
² Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, Japan.
³ Department of Gynecology, Cancer Institute Hospital of JFCR, Tokyo, Japan.
⁴ Department of Obstetrics and Gynecology, Kurume University Hospital, Fukuoka, Japan.
⁵ Department of Gynecologic Oncology, Aichi Cancer Center Hospital, Aichi, Japan.
⁶ Department of Obstetrics and Gynecology, University of Tsukuba Hospital, Ibaraki, Japan.
⁷ Division of Gynecologic Oncology, Hokkaido Cancer Center, Hokkaido, Japan.
⁸ Department of Obstetrics and Gynecology, Ehime University Hospital, Ehime, Japan.
⁹ Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
¹⁰ Division of Gynecologic Cancer, Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
¹¹ Institute of Clinical Medicine, National Yang Ming Chiao Tung University; Department of Obstetrics and Gynecology, Taipei Veterans General Hospital; Female Cancer Foundation, Taipei, Taiwan; China Medical University Hospital, Taichung, Taiwan.
¹² Department of Obstetrics and Gynecology, Linkou Chang Gung Memorial Hospital and Chang Gung University Medical College, Kueishan, Taoyuan City, Taiwan.
¹³ Oncology Science Unit, MSD K.K., Tokyo, Japan.
¹⁴ Biostatistics & Research Decision Sciences, MSD K.K., Tokyo, Japan.
¹⁵ Eisai Inc., Nutley, NJ, USA.
¹⁶ Global Clinical Development, Merck & Co., Inc., Rahway, NJ, USA.
¹⁷ Clinical Oncology, Eisai Co., Ltd., Tokyo, Japan.
¹⁸ Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
¹⁹ Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan, Seoul, Korea.

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.

Trial registration: ClinicalTrials.gov Identifier: NCT03517449.

Keywords: Asian; Chemotherapy; Drug Therapy, Combination; Endometrial Cancer; Immunotherapy; Survival.

Publication types

Randomized Controlled Trial
Research Support, N.I.H., Extramural

MeSH terms

Antibodies, Monoclonal, Humanized*
Antineoplastic Combined Chemotherapy Protocols
Asia, Eastern / epidemiology
Endometrial Neoplasms* / drug therapy
Endometrial Neoplasms* / etiology
Female
Humans
Neoplasm Recurrence, Local / drug therapy
Neoplasm Recurrence, Local / etiology
Phenylurea Compounds*
Physicians*
Quinolines*

Substances

pembrolizumab
lenvatinib
Phenylurea Compounds
Quinolines
Antibodies, Monoclonal, Humanized

Associated data

ClinicalTrials.gov/NCT03517449

Grants and funding

P30 CA008748/CA/NCI NIH HHS/United States