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

Authors
Christian Marth,Richard Moore
Mariusz Bidziński,Sandro Pignata,Ali Ayhan,María Rubio,Mario Beiner,Marcia Hall,Christof Vulsteke,Elena Braicu,Kenzo Sonoda,Xiaohua Wu,Sophia Frentzas,André Mattar,Stéphanie Lheureux,Xiaojun Chen,Kosei Hasegawa,Manuel Magallanes-Maciel,Chel Choi,Mariia Shalkova,Diego Kaen,Peng‐Hui Wang,Regina Berger,Chinyere Okpara,Jodi McKenzie,Lili Yao,Robert Orlowski,Vivek Khemka,Lucy Gilbert,Vicky Makker,G. Abuin,Liliana Zamora,Margarita Alfie,Ignacio Casarini,Michelle Harrison,Sumitra Ananda,Catherine Shannon,Michael Friedländer,Tarek Meniawy,Bo Gao,Sally Baron‐Hay,Connie Diakos,Stephan Polterauer,Edgar Petru,Marlies Bock,Jean‐François Baurain,Toon Gorp,Sevilay Altıntaş,João Lima,Ruffo Freitas‐Júnior,RO Sant'ana,Andréia Melo,Fábio Franke,Graziela Molin,Fernanda Damian,João Guedes,Susan Ellard,Anna Tinker,Vanessa Samouëlian,Suzanne Fortin,Paul Bessette,Michael Kolinsky,Nidhi Tyagi,Josée-Lyne Ethier,Helen Mackay,Charles Lim,Lingya Pan,Ruifang An,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,F Marmé,Karen Cadoo,Jacob Korach,Talia Levy,Amnon Amit,Paolo Scollo,Emanuele Naglieri,Claudio Zamagni,Vanda Salutari,Tomoka Usami,Kazuto Nakamura,Koji Matsumoto,Wataru Yamagami,Yoichi Kobayashi,Masashi Takano,Hidenori Kato,Akira Kikuchi,Noriyuki Katsumata,Shoji Kamiura,Koji Horie,Takuya Tsunoda,Nao Suzuki,Mayu Yunokawa,Shin Nishio,Wataru Kudaka,Francisco Cabrera,R. Mendoza,Manuel Maciel,Ricardo Villalobos-Valencia,Jose Penagos,Yamil Chuken,Beata Maćkowiak-Matejczyk,R. Tarnawski,Ewa Kalinka‐Warzocha,Wiesława Bednarek,Anna Dańska-Bidzińska,P. Koralewski,A. Roszak,А. Кедрова,Natalia Musaeva,А Урманчеева,Aleksandr Vasiliev,Sufia Safina,Alla Lisyanskaya,I. Rykov,А. Rumyantsev,А. Белоногов,Yulia Makarycheva,Yong Kim,Hee Kim,Sang Kim,Marı́a Varela,Antonio Casado,Tamara Redondo,M.J. Pérez,Margarita Romeo,Ignacio Noguera,Álvaro Garcia,Wu-Chou Lin,Hung-Hsueh Chou,Wen‐Fang Cheng,Chien‐Hsing Lu,Tayup Şimşek,Fatih Köse,Mehmet Vardar,Kemal Özerkan,Alun Hughes,Alison Stillie,Gemma Eminowicz,Saira Khalique,Олена Сухіна,Tetiana Piatnytska,Hanna Averina,Yaroslav Kulyaba,Anna Kryzhanivska,Igor Bondarenko,V Svintsitsky,Yuliia Krasnohrud,Олександр Войтко,Joseph Buscema,Sharad Ghamande,Sharyn Lewin,Deena Graham,Maria Bell,Alessandro Santin,Christine Lee,Stephanie Blank,Gottfried Konecny,Bradley Corr,Linda Le,Jennifer Scalici,Charles Anderson,Patricia Braly,Julia Fehniger,Gina Westhoff,Lauren Bollinger
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Published
Nov 26, 2024
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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.

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