Lenvatinib Plus Pembrolizumab and Chemotherapy Versus Chemotherapy in Advanced Metastatic Gastroesophageal Adenocarcinoma: The Phase III, Randomized LEAP-015 Study

作者：Kohei Shitara, Sylvie Lorenzen, Jin Li, Yuxian Bai, M. Fernández, Mynor Aguilar, Hirokazu Shoji, Felipe Reyes-Cosmelli, Yamilé Peña, Luis Corrales, Lucjan Wyrwicz, Daniel Acosta Eyzaguirre, Yueyin Pan, Min‐Hee Ryu, Deirdre J. Cohen, Zev A. Wainberg, Geoffrey Ku, Josep Tabernero, Eric Van Cutsem, Shukui Qin, Do‐Youn Oh, Jianming Xu, Li Liang, Sonal Bordia, Pooja Bhagia, Sun Young Rha, on behalf of the LEAP-015 Investigators, Ezequiel Slutsky, Juan Cundom, Andrea Gabriela Soria, Marcela Carballido, Juan Manuel O’Connor, Julieta Grasseli, Matthew Burge, Daniel Paul Brungs, Muhammad Adnan Khattak, Karen Geboes, Eric Van Cutsem, Jeroen Dekervel, Lionel D. Hondt, Frédéric Lemay, Rosalyn A. Juergens, Felipe Reyes, Gonzalo Pizarro Brito, Maria Alejandra Ojeda, Hiwot Araya, Patricio Yañez, Jianwei Yang, Xi Chen, Yuxian Bai, Hongming Pan, Nong Xu, Yueyin Pan, Qinghong Guo, Baorui Liu, Feng Ye, Xin Wang, Qi Li, Yong Tang, Huiting Xu, Haichuan Su, Ying Cheng, Xianli Yin, Qun Zhao, Ning Li, Jun You, Yi Ba, Jiang We, Lin Shen, Jin Li, Wangjun Liao, Zhen Li, Lei Yang, Yamilé Peña, Iván Bustillo, Carlos Jose Narvaez, Manuel Enrique Gonzalez Fernandez, Raimundo Manneh, Ana Iris Arias, Luis Corrales, Andres Wiernik Rodriguez, T. Aparicio, Y. Touchefeu, Helene Boussion-Desloges, Laurent Mineur, Christophe Tournigand, François Ghiringhelli, Marie Pierre Galais, Eric Terrebonne, Thomas Walter, Mathieu Baconnier, Sylvie Lorenzen, Eray Goekkurt, Annika Kurreck, Arne Kandulski, Thorsten Oliver Goetze, Florian Lordick, Mynor Aguilar, Karla Alejandra Lopez, Rixci Augusto Lenin Ramirez Fallas, Pier Anyelo Ramos Elias, Juan Pablo Moreira, Wing Lok Wendy Chan, Ashely Cheng, Winnie Yeo, Maeve A. Lowery, Adrian Murphy, Sharon Pelles Avraham, Ayala Hubert, Irit Ben‐Aharon, Valeriya Semenisty, Gali Perl, Wael Hozaeel, Armando Santoro, Elena Aurelia Mazza, Ferdinando De Vita, G. Aprile, Giovanni Gerardo Cardellino, Filippo Pietrantonio, Pierfrancesco Tassone, Kohei Shitara, Hirokazu Shoji, Yukiya Narita, Hiroki Hara, Kensei Yamaguchi, Naotoshi Sugimoto, Nozomu Machida, Tomohiro Nishina, Akihito Tsuji, Yasuhiro Choda, Kenji Amagai, Masahiro Tsuda, Shogen Boku, Boguslawa Karaszewska, Kamil Kuć, Jacek Mackiewicz, Lucjan Wyrwicz, Łukasz Hajac, A A Tryakin, Dmitry Nosov, Р. В. Орлова, А. М. Карачун, Michael Osipov, М. В. Копп, Natalia Fadeeva, Nikolay Kislov, Sun Young Rha, Seung Tae Kim, Min‐Hee Ryu, Do‐Youn Oh, Keun-Wook Lee, Hei‐Cheul Jeung, Jonggwon Choi, Sang Cheul Oh, Paula Jiménez Fonseca, F. Rivera Herrero, Pilar Aitana Calvo Ferrandiz, Daniel Acosta Eyzaguirre, Kun‐Huei Yeh, Jen‐Shi Chen, Li‐Yuan Bai, Chia‐Jui Yen, Bülent Erdoğan, Pınar Gürsoy, Mustafa Özgüroğlu, Şuayib Yalçın, Umut Demırcı, Mehmet Bilici, İlhan Hacıbekiroğlu, Hugo Ford, Kai‐Keen Shiu, Martin Scott-Brown, Russell Petty, Wasat Mansoor, Zev A. Wainberg, Marcus Smith Noel, Peter C. Enzinger, Sreenivasa R Chandana, Geoffrey Ku, Dierdre Cohen, Vincent K. Lam · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco-25-00748 · 被引用次数：18 · 研究领域：Esophageal Cancer Research and Treatment、Cancer Immunotherapy and Biomarkers、Gastric Cancer Management and Outcomes

PURPOSE The phase III randomized open-label LEAP-015 study (ClinicalTrials.gov identifier: NCT04662710 ) evaluated first-line lenvatinib plus pembrolizumab and chemotherapy versus chemotherapy for advanced metastatic gastroesophageal adenocarcinoma. METHODS Eligible participants 18 years and older with untreated human epidermal growth factor receptor 2–negative locally advanced unresectable or metastatic gastroesophageal adenocarcinoma were randomly assigned 1:1 to induction with oral lenvatinib 8 mg once daily plus pembrolizumab 400 mg intravenously once every 6 weeks (×2) and investigators’ choice of capecitabine and oxaliplatin once every 3 weeks (×4) or fluorouracil, leucovorin, and oxaliplatin once every 2 weeks (×6) and consolidation with lenvatinib plus pembrolizumab, or chemotherapy. Dual primary end points were progression-free survival (PFS) and overall survival (OS) in participants with PD-L1 combined positive score (CPS) ≥1 and all participants. Secondary end points included objective response rate (ORR) and duration of response. RESULTS Of 880 participants randomly assigned, 443 received lenvatinib plus pembrolizumab and 437 received chemotherapy. The median follow-ups were 32.2 months (range, 19.0-41.7) in participants with PD-L1 CPS ≥1 and 31.8 months (19.0-41.7) in all participants. At interim analysis, PFS was statistically significant with lenvatinib plus pembrolizumab versus chemotherapy in participants with PD-L1 CPS ≥1 (median, 7.3 v 6.9 months; hazard ra...