First-Line Lenvatinib Plus Pembrolizumab Versus Chemotherapy for Advanced Endometrial Cancer: A Randomized, Open-Label, Phase III Trial

作者：Christian Marth, Richard G. Moore, Mariusz Bidziński, Sandro Pignata, Ali̇ Ayhan, María Jesús Rubio, Mario E. Beiner, Marcia Hall, Christof Vulsteke, Elena Ioana Braicu, Kenzo Sonoda, Xiaohua Wu, Sophia Frentzas, André P. L. Mattar, Stéphanie Lheureux, Xiaojun Chen, Kosei Hasegawa, Manuel Ernesto Magallanes-Maciel, Chel Hun Choi, Mariia Shalkova, Diego Lucas Kaen, Peng‐Hui Wang, Regina Berger, Chinyere E. Okpara, Jodi A. McKenzie, Lili Yao, Robert J. Orlowski, Vivek Khemka, Lucy Gilbert, Vicky Makker, on behalf of the ENGOT-en9/LEAP-001 Investigators, Diego Lucas Kaen, Gonzalo Gómez Abuin, Liliana Beatriz Zamora, Margarita Sonia Alfie, Ignacio Casarini, Michelle Harrison, Sumitra S. Ananda, Catherine Shannon, Sophia Frentzas, Michael J. Friedlander, Tarek M. Meniawy, Bo Gao, Sally E. Baron-Hay, Connie Irene Diakos, Christian Marth, Stephan Polterauer, Edgar Petru, Marlies De Bock, Christof Vulsteke, Jean‐François Baurain, Toon Van Gorp, Sevilay Altıntaş, João Paulo da Silveira Nogueira Lima, André P. L. Mattar, Ruffo de Freitas Junior, RO de Sant'ana, Andréia Cristina de Melo, Fabio Andre Franke, Graziela Zibetti Dal Molin, Fernanda Damian, João Daniel Guedes, Susan L. Ellard, Anna V. Tinker, Vanessa Samouëlian, Suzanne Fortin, Paul Bessette, Michael Paul Kolinsky, Nidhi Kumar Tyagi, Josée-Lyne Ethier, Lucy Gilbert, Stéphanie Lheureux, Helen J MacKay, Charles Henry Lim, Xiaohua Wu, Lingya Pan, Ruifang An, Xiaojun Chen, Hong Zheng, Yumei Wu, Jianqing Zhu, Shuzhong Yao, Xuemei Jia, Yi Huang, Weiguo Lv, Yu Zhang, Qi Zhou, Cailing Ma, Radoslav Chekerov, Paweł Mach, Ralf Witteler, Frederik Marmè, Karen Cadoo, Jacob Korach, Talia Levy, Mario E. Beiner, Amnon Amit, Paolo Scollo, Emanuele Naglieri, Sandro Pignata, Claudio Zamagni, Vanda Salutari, Tomoka Usami, Kazuto Nakamura, Koji Matsumoto, Wataru Yamagami, Yoichi Kobayashi, Masashi Takano, Hidenori Kato, Kenzo Sonoda, Akira Kikuchi, Noriyuki Katsumata, Shoji Kamiura, Koji Horie, Kosei Hasegawa, Takuya Tsunoda, Nao Suzuki, Mayu Yunokawa, Shin Nishio, Wataru Kudaka, Fernando Felix Guerrero Cabrera, Rene Lazaro Gonzalez Mendoza, Manuel Ernesto Magallanes Maciel, Ricardo Villalobos-Valencia, Jose Escobar Penagos, Yamil Alonso Lopez Chuken, Beata Maćkowiak-Matejczyk, Rafal Tarnawski, Ewa Kalinka‐Warzocha, Mariusz Bidziński, Wiesława Bednarek, Anna Dańska-Bidzińska, P. Koralewski, A. Roszak, А. Г. Кедрова, Natalia E. Musaeva, А Ф Урманчеева, Aleksandr Vasiliev, Sufia Safina, Alla Sergeevna Lisyanskaya, I. V. Rykov, А. А. Rumyantsev, А. В. Белоногов, Yulia Makarycheva, Yong Man Kim, Chel Hun Choi, Yong Beom Kim, Hee Seung Kim, Sang Wun Kim, Maria Quindos Varela, Antonio Casado Herraez, Tamara Díaz Redondo, M.J. Rubio Pérez, Margarita Romeo Marin, Ignacio Romero Noguera, Álvaro Taus Garcia, Wu-Chou Lin, Hung‐Hsueh Chou, Wen‐Fang Cheng, Chien‐Hsing Lu, Peng-Hui Wang, Tayup Şimşek, Fatih Köse, Ali̇ Ayhan, Mehmet Ali Vardar, Kemal Özerkan, Andrew Hughes, Alison L. Stillie, Gemma Eminowicz, Saira Khalique, Mariia Shalkova, Олена Миколаївна Сухіна, Tetiana Piatnytska, Hanna Averina, Yaroslav Kulyaba, Anna Kryzhanivska, Igor Bondarenko, V S Svintsitsky, Yuliia Krasnohrud, Nataliia Voitko, Joseph Buscema, Sharad A. Ghamande, Sharyn Nan Lewin, Deena M. Graham, Vicky Makker, Maria C. Bell, Alessandro Davide Santin, Christine Lee, Stephanie V. Blank, Gottfried E. Konecny, Bradley R. Corr, Linda Van Le, Richard G. Moore, Jennifer Michelle Scalici, Charles E. Anderson, Patricia D. Braly, Julia Fehniger, Gina L. Westhoff, Lauren E. Bollinger · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco-24-01326 · 被引用次数：66 · 研究领域：Endometrial and Cervical Cancer Treatments、Cancer Immunotherapy and Biomarkers、Cervical Cancer and HPV Research

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...