First-Line Lenvatinib Plus Pembrolizumab Versus Chemotherapy for Advanced Endometrial Cancer: A Randomized, Open-Label, Phase III Trial
Authors: Christian Marth, Richard G. Moore, Mariusz Bidziński, Sandro Pignata, Ali Ayhan, M. Jesús Rubio, Mario Beiner, Marcia Hall, Christof Vulsteke, Elena Ioana Braicu, Kenzo Sonoda, Xiaohua Wu, Sophia Frentzas, André Mattar, Stephanie Lheureux, Xiaojun Chen, Kosei Hasegawa, Manuel Magallanes-Maciel, Chel Hun Choi, Mariia Shalkova, Diego Kaen, Peng-Hui Wang, Regina Berger, Chinyere E. Okpara, Jodi McKenzie, Lili Yao, Robert Orlowski, Vivek Khemka, Lucy Gilbert, Vicky Makker, Diego Lucas Kaen, Gonzalo Gomez Abuin, Liliana Beatriz Zamora, Margarita Sonia Alfie, Ignacio Alfredo Casarini, Michelle Harrison, Sumitra Ananda, Catherine Margaret Shannon, Sophia Frentzas, Michael Friedlander, Tarek Meniawy, Bo Gao, Sally Baron-Hay, Connie Diakos, Christian Marth, Stephan Polterauer, Edgar Petru, Marlies De Bock, Christof Vulsteke, Jean-Francois Baurain, Toon Van Gorp, Sevilay Altintas, Joao Paulo da Silveira Nogueira Lima, Andre Mattar, Ruffo de Freitas Junior, Rosane O. Santana, Andreia Cristina de Melo, Fabio Andre Franke, Graziela Zibetti Dal Molin, Fernanda Bronzon Damian, João Daniel Cardoso Guedes, Susan Ellard, Anna Tinker, Vanessa Samouëlian, Suzanne Fortin, Paul Bessette, Michael Kolinsky, Nidhi Kumar Tyagi, Josee-Lyne Ethier, Lucy Gilbert, Stephanie Lheureux, Helen MacKay, Charles 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, Pawel Mach, Ralf Witteler, Frederik Marmè, Karen Cadoo, Jacob Korach, Talia Levy, Mario Beiner, Amit Amnon, 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 Mackowiak-Matejczyk, Rafal Tarnawski, Ewa Kalinka, Mariusz Bidzinski, 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, 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, Margarita Romeo Marin, Ignacio Romero Noguera, Alvaro Taus Garcia, Wu-Chou Lin, Hung-Hsueh Chou, Wen-Fang Cheng, Chien-Hsing Lu, Peng-Hui Wang, Tayup Simsek, Fatih Kose, Ali Ayhan, Mehmet Ali Vardar, Kemal Ozerkan, Andrew Hughes, Alison Stillie, Gemma Eminowicz, Saira Khalique, Mariia Shalkova, Olena Sukhina, Tetiana Piatnytska, Hanna Averina, Yaroslav Kulyaba, Anna Kryzhanivska, Igor Bondarenko, Valentyn Svintsitsky, Yuliia Krasnohrud, Nataliia Voitko, Joseph Buscema, Sharad Ghamande, Sharyn Lewin, Deena M. Graham, Vicky Makker, Maria Bell, Alessandro Santin, Christine Lee, Stephanie Blank, Gottfried E. Konecny, Bradley Corr, Linda Van Le, Richard G. Moore, Jennifer Scalici, Charles Anderson, Patricia Braly, Julia Fehniger, Gina Westhoff, Lauren Bollinger
Journal: Journal of Clinical Oncology (2024)

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.