First-Line Lenvatinib Plus Pembrolizumab Versus Chemotherapy for Advanced Endometrial Cancer: A Randomized, Open-Label, Phase III Trial
Abstract
PURPOSE Lenvatinib plus pembrolizumab (len + pembro) significantly improved progression-free survival (PFS) and overall survival (OS) versus chemotherapy in previously treated advanced or recurrent endometrial cancer (aEC) in the phase III Study 309/KEYNOTE-775. We report results from the phase III, randomized, open-label European Network of Gynaecological Oncological Trial-en9/LEAP-001 study (ClinicalTrials.gov identifier: NCT03884101 ) that evaluated len + pembro versus chemotherapy in first-line aEC. METHODS Patients with stage III to IV or recurrent, radiographically apparent EC and no previous chemotherapy or disease progression ≥6 months after neo/adjuvant platinum-based chemotherapy were randomly assigned 1:1 to lenvatinib 20 mg once daily plus pembrolizumab 200 mg once every 3 weeks or paclitaxel 175 mg/m 2 plus carboplatin AUC 6 mg/mL/min once every 3 weeks. Primary end points were PFS and OS, evaluated in the mismatch repair-proficient (pMMR) and all-comers populations. Noninferiority was assessed for OS at final analysis (FA) for len + pembro versus chemotherapy (multiplicity-adjusted, one-sided nominal alpha, .0159; null hypothesis–tested hazard ratio [HR], 1.1). RESULTS Eight hundred forty-two patients were randomly assigned (len + pembro, n = 420 [pMMR population, n = 320]; chemotherapy, n = 422 [pMMR population, n = 322]). At FA (data cutoff, October 2, 2023), median PFS (95% CI) in the pMMR population was 9.6 (8.2 to 11.9) versus 10.2 (8.4 to 10.5) months with len + pembro versus chemotherapy (hazard ratio [HR], 0.99 [95% CI, 0.82 to 1.21]) and among all-comers was 12.5 (10.3 to 15.1) versus 10.2 (8.4 to 10.4) months (HR, 0.91 [95% CI, 0.76 to 1.09]; descriptive analyses). Median OS (95% CI) in the pMMR population was 30.9 (25.4 to 37.7) versus 29.4 (26.2 to 35.4) months with len + pembro versus chemotherapy (HR, 1.02 [95% CI, 0.83 to 1.26]; noninferiority P = .246, not statistically significant per multiplicity control strategy) and among all-comers was 37.7 (32.2 to 43.6) versus 32.1 (27.2 to 35.7) months (HR, 0.93 [95% CI, 0.77 to 1.12]). Grade ≥3 treatment-related adverse events occurred in 331/420 (79%) versus 274/411 (67%) treated patients. CONCLUSION First-line len + pembro did not meet prespecified statistical criteria for PFS or OS versus chemotherapy in pMMR aEC.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (179)
M. Jesús Rubio
H. Reina Sofía de Córdoba and GEICO Group, Córdoba, Spain
Marcia Hall
Mount Vernon Cancer Centre, Northwood, United Kingdom
Elena Ioana Braicu
Department of Gynecology, Campus Virchow, Charité Universitätsmedizin Berlin and North Eastern German Society for Gynecologic Oncology (NOGGO), Berlin, Germany
Manuel Magallanes-Maciel
Centro Oncologico Internacional, Mexico City, Mexico
Diego Kaen
Centro Oncologico Riojano Integral and National University of La Rioja, La Rioja, Argentina
Regina Berger
Medical University Innsbruck, Department for Gynecology and Obstetrics, and AGO Austria Study Center, Innsbruck, Austria
Chinyere E. Okpara
Eisai Ltd., Hatfield, United Kingdom
Jodi McKenzie
Clinical Development, Eisai Inc., Nutley, NJ
Lili Yao
Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science
Robert Orlowski
University of Texas M.D. Anderson Cancer Center, Houston
Vivek Khemka
Merck & Co, Inc, Rahway, NJ
Diego Lucas Kaen
Gonzalo Gomez Abuin
Liliana Beatriz Zamora
Margarita Sonia Alfie
Organizacion Medica de Investigacion, Buenos Aires, Argentina
Ignacio Alfredo Casarini
Michelle Harrison
Sumitra Ananda
Peter MacCallum Cancer Centre and Epworth Healthcare, Melbourne, Australia
Catherine Margaret Shannon
Sophia Frentzas
Department of Medical Oncology, Monash Health, Clayton, VIC, Australia
Michael Friedlander
Tarek Meniawy
Saint John of God Subiaco Hospital, Subiaco, Western Australia, Australia
Bo Gao
College of Energy, Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory of Advanced Negative Carbon Technologies, Soochow University, Suzhou, China.
Sally Baron-Hay
Connie Diakos
Christian Marth
Stephan Polterauer
Edgar Petru
Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria
Marlies De Bock
Christof Vulsteke
Integrated Cancer Center Ghent, AZ Maria Middelares, Ghent, Belgium
Jean-Francois Baurain
St. LUC University Hospital Medical School, Woluwe-Saint-Lambert, Belgium
Toon Van Gorp
Sevilay Altintas
Joao Paulo da Silveira Nogueira Lima
André Mattar
Mastology Department, Women’s Health Hospital, São Paulo
Ruffo de Freitas Junior
Rosane O. Santana
Andreia Cristina de Melo
Fabio André Franke
Oncosite-Oncoclínicas, Ijuí, Brazil
Graziela Zibetti Dal Molin
Fernanda Bronzon Damian
Centro de Pesquisa em Oncologia (CPO) - Hospital São Lucas da PUCRS, Porto Alegre, Brazil
Joao Daniel Cardoso Guedes
Susan Ellard
Anna Tinker
BC Cancer, Vancouver, BC, Canada
Vanessa Samouëlian
Gynecologic Oncology, Centre Hospitalier de l’Université de Montréal (CHUM), Centre de Recherche de l’Université de Montréal (CRCHUM), Université de Montréal, Montreal, QC, Canada
Suzanne Fortin
Paul Bessette
Michael Kolinsky
Nidhi Kumar Tyagi
Josee-Lyne Ethier
Sunnybrook Odette Cancer Centre, Toronto, ON, Canada
Lucy Gilbert
Department of Oncology, McGill University Health Centre, Montreal
Stephanie Lheureux
Helen Mackay
Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
Charles Lim
Xiaohua Wu
Fudan University Shanghai Cancer Center Shanghai China
Lingya Pan
Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
Ruifang An
The First Affiliated Hospital of Xi’an Jiaotong University Xi’an China
Xiaojun Chen
Hong Zheng
Center of Nanomaterials for Renewable Energy, State Key Laboratory of Electrical Insulation and Power Equipment, School of Electrical Engineering
Yumei Wu
Jianqing Zhu
Zhejiang Cancer Hospital Hangzhou China
Shuzhong Yao
Department of Gynecology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Xuemei Jia
Department of Gynecology, Women’s Hospital of Nanjing Medical University (Nanjing Women and Children’s Healthcare Hospital)
Yi Huang
Hubei Cancer Hospital Wuhan China
Weiguo Lv
Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Yu Zhang
Xiangya Hospital, Central South University Changsha China
Qi Zhou
Chongqing University Cancer Hospital Chongqing China
Cailing Ma
Radoslav Chekerov
Pawel Mach
Ralf Witteler
University Hospital Münster, Münster, Germany
Frederik Marmé
Faculty of Medicine Mannheim, Department of Obstetrics and Gynecology, University of Heidelberg, Mannheim, Germany
Karen Cadoo
Jacob Korach
ISGO and Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel
Talia Levy
Mario Beiner
Meir Medical Center, Kfar Saba, Israel
Amit Amnon
Paolo Scollo
Maternal and Child Department, Obstetrics and Gynecology Cannizzaro Hospital of Catania, Kore University of Enna, Catania, Italy
Emanuele Naglieri
Sandro Pignata
Uro-Gynecologic Oncology Unit, Istituto Nazionale Tumori IRCCS-Fondazione “G. Pascale,” Naples, Italy
Claudio Zamagni
IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
Vanda Salutari
Department of Women, Children and Public Health Sciences, Gynecologic Oncology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Tomoka Usami
Kazuto Nakamura
Koji Matsumoto
Hyogo Cancer Center, Akashi, Hyogo, Japan
Wataru Yamagami
Yoichi Kobayashi
Masashi Takano
Hidenori Kato
Hokkaido Cancer Society, Hokkaido, Japan
Kenzo Sonoda
Gynecology Service, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
Akira Kikuchi
Noriyuki Katsumata
Shoji Kamiura
Koji Horie
Kosei Hasegawa
Takuya Tsunoda
Nao Suzuki
Mayu Yunokawa
Department of Advanced Medical Development, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
Shin Nishio
Department of Obstetrics and Gynecology, Kurume University, Fukuoka, Japan
Wataru Kudaka
Fernando Felix Guerrero Cabrera
Rene Lazaro Gonzalez Mendoza
Manuel Ernesto Magallanes Maciel
Ricardo Villalobos Valencia
Centro Medico Dalinde, Mexico City, Mexico
Jose Escobar Penagos
Yamil Alonso Lopez Chuken
Beata Mackowiak-Matejczyk
Rafal Tarnawski
Ewa Kalinka
Mariusz Bidzinski
Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
Wieslawa Bednarek
Anna Danska-Bidzinska
Piotr Koralewski
Andrzej Roszak
Anna Kedrova
Natalia Musaeva
Adiliya Fettekhovna Urmancheeva
Aleksandr Gennadievich Vasiliev
Sufia Zievna Safina
Alla Sergeevna Lisyanskaya
Ivan V. Rykov
Alexey Alexandrovich Rumyantsev
Aleksandr Belonogov
Yulia Makarycheva
Yong Man Kim
Asan Medical Center, University of Ulsan, Seoul, South Korea
Chel Hun Choi
Yong Beom Kim
Hee Seung Kim
Sang Wun Kim
Maria Quindos Varela
Antonio Casado Herraez
Tamara Diaz Redondo
Maria Jesus Rubio Perez
Medical Oncology Department, Maimonides Biomedical Reserach Institute of Cordoba (IMIBIC), University of Cordoba (UCO), Hospital Universitario Reina Sofia, Cordoba, Spain
Margarita Romeo Marin
Ignacio Romero Noguera
Alvaro Taus Garcia
Wu-Chou Lin
Hung-Hsueh Chou
Wen-Fang Cheng
Chien-Hsing Lu
Department of Obstetrics and Gynecology, Taichung Veteran General Hospital, Taichung, Taiwan
Peng-Hui Wang
Taipei Veterans General Hospital, Taipei, Taiwan
Tayup Simsek
Fatih Kose
Ali Ayhan
Turkish Society of Gynecologic Oncology (TRSGO), Başkent University, Ankara, Turkey
Mehmet Ali Vardar
Medical Faculty, Department of Obstetrics and Gynecology, University of Cukurova, and Department of Gynecologic Oncology, Balcalı Hospital, Adana, Turkey
Kemal Ozerkan
Andrew Hughes
Alison Stillie
Edinburgh Cancer Centre, Western General Hospital, Edinburgh, United Kingdom
Gemma Eminowicz
Saira Khalique
Mariia Shalkova
Communal Non-Profit Enterprise Regional Center of Oncology, Kharkiv, Ukraine
Olena Sukhina
Tetiana Piatnytska
Hanna Averina
Yaroslav Kulyaba
Anna Kryzhanivska
Igor Bondarenko
Dniprovsky State Medical University, Dnipro, Ukraine
Valentyn Svintsitsky
Yuliia Krasnohrud
Nataliia Voitko
Joseph Buscema
Arizona Oncology, Tucson, AZ
Sharad Ghamande
Sharyn Lewin
Deena M. Graham
Vicky Makker
Maria Bell
Alessandro Santin
Yale School of Medicine, Division of Gynecologic Oncology, New Haven, CT
Christine Lee
Stephanie Blank
Gottfried E. Konecny
Bradley Corr
University of Colorado, Aurora, CO
Linda Van Le
Richard G. Moore
Division of Gynecologic Oncology, Wilmot Cancer Institute, Department of Obstetrics and Gynecology, University of Rochester, Rochester, NY
Jennifer Scalici
Charles Anderson
Providence Sacred Heart Children's Hospital, Spokane, Washington, United States
Patricia Braly
Julia Fehniger
Gina Westhoff
Lauren Bollinger