@article{2b65c7b76ab14710b367b519ece747cb,
title = "Lenvatinib plus pembrolizumab in Japanese patients with endometrial cancer: Results from Study 309/KEYNOTE-775",
abstract = "Study 309/KEYNOTE-775 is a phase 3 open-label, randomized trial of lenvatinib plus pembrolizumab versus treatment of physician's choice (TPC) in patients with advanced endometrial cancer with progression after platinum-based therapy. Primary endpoints of superiority for lenvatinib plus pembrolizumab were met for progression-free survival (PFS) and overall survival (OS) in all-comers (ie, regardless of mismatch repair [MMR] status) and patients with MMR proficiency (pMMR). We present results for the Japanese subset. Patients were randomized to oral lenvatinib 20 mg/day plus intravenous pembrolizumab 200 mg every 3 weeks (Q3W; up to 35 cycles of pembrolizumab) or TPC (intravenous doxorubicin 60 mg/m2 Q3W or paclitaxel 80 mg/m2 QW [3 weeks on/1 week off]). Primary endpoints were PFS by blinded independent central review per RECIST version 1.1 and OS. One hundred four patients were randomized in Japan (data cutoff, October 26, 2020; median follow-up, 11.8 [range, 1.1–26.9] months). Hazard ratios (HRs) for PFS with lenvatinib plus pembrolizumab versus TPC were 1.04 (95% CI, 0.63–1.73) in patients with pMMR and 0.81 (0.50–1.31) in all-comers. Hazard ratios for OS were 0.74 (0.41–1.34) with pMMR and 0.59 (0.33–1.04) for all-comers. Adverse events were manageable and led to discontinuation of one/both study drugs in 36.5% of patients in the lenvatinib plus pembrolizumab group versus 7.8% in the TPC group. Similar to the global Study 309/KEYNOTE-775 results, this analysis suggested favorable efficacy and manageable safety with lenvatinib plus pembrolizumab after platinum-based chemotherapy in Japanese patients with advanced endometrial cancer and supports this combination as a new standard of care in this population.",
keywords = "Japan, endometrial cancer, lenvatinib, pembrolizumab, treatment outcomes",
author = "Kan Yonemori and Mayu Yunokawa and Kimio Ushijima and Jun Sakata and Ayumi Shikama and Shinichiro Minobe and Tomoka Usami and Takayuki Enomoto and Kazuhiro Takehara and Kosei Hasegawa and Wataru Yamagami and Keiko Yamamoto and Shirong Han and Lea Dutta and Robert Orlowski and Takuma Miura and Vicky Makker and Keiichi Fujiwara",
note = "Funding Information: Kan Yonemori has received lecture fees from Eisai, Pfizer, Eli Lilly, Takeda, Chugai, and AstraZeneca and research funding from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Daiichi‐Sankyo, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Seattle Genetics, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirin, Nihon Kayaku, and Haihe. Kimio Ushijima has received research funding from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Takayuki Enomoto has received honoraria from AstraZeneca, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Takeda, and Chugai. Kazuhiro Takehara has received lecture fees, honoraria, or other fees from Takeda. Kosei Hasegawa has received lecture fees, honoraria, or other fees from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Keiko Yamamoto and Shirong Han are employees of MSD K.K., Tokyo, Japan. Lea Dutta is an employee of Eisai Inc., Woodcliff Lake, NJ, USA. Robert Orlowski is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and owns stock in Merck & Co., Inc., Rahway, NJ, USA. Takuma Miura is an employee of Eisai Co., Ltd., Tokyo, Japan. Vicky Makker has received study support (all funding to institution) from AstraZeneca, Clovis, Eisai, Karyopharm, Mereo, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Takeda, and Zymeworks. Keiichi Fujiwara has received research funding from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and Eisai. The study was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and Eisai Inc., Woodcliff Lake, NJ, USA. All authors had access to the data from the study and had final responsibility for the decision to submit for publication. All other authors have no conflicts of interest. Funding Information: We thank the patients and their families and caregivers for participating in this study, along with all investigators and site personnel. Contributions to the study design were provided by Steve Keefe, Gursel Aktan, and Greg Lubiniecki, all of Merck & Co., Inc., Rahway, NJ, USA, and by Jodi Mckenzie of Eisai Inc., Woodcliff Lake, NJ, USA; and contributions to data collection were provided by Elizabeth Rafeiro, of Merck & Co., Inc., Rahway, NJ, USA. Medical writing assistance was provided by Rozena Varghese, PharmD, CMPP, and Christabel Wilson, MSc, of ICON plc (Blue Bell, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and Eisai Inc., Woodcliff Lake, NJ, USA. A portion of these data have been presented at the 63rd Annual Meeting of the Japan Society of Gynecologic Oncology, July 16–18, 2021; and at the 7th Biennial Meeting of the Asian Society of Gynecologic Oncology, November 25–27, 2021. Publisher Copyright: {\textcopyright} 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.",
year = "2022",
month = oct,
doi = "10.1111/cas.15436",
language = "English",
volume = "113",
pages = "3489--3497",
journal = "Cancer science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
number = "10",
}
