VIKTORIA-1 Trial of Gedatolisib Plus Fulvestrant With or Without Palbociclib in Hormone Receptor–Positive/HER2−/PIK3CA Wild-Type Advanced Breast Cancer

作者：Sara A. Hurvitz, Rachel M. Layman, Giuseppe Curigliano, Fabrice André, Massimo Cristofanilli, Sung-Bae Kim, J. Martinez Rodriguez, Jorge Nadal, G. Kim, Louisa L. Lo, Yuly A. Remolina-Bonilla, Geronimo Rosselli, George Emile, Ernesto Korbenfeld, Juan Manuel Puig, Robert Wesolowski, Miguel Martin, Alistair Ring, Hyo S. Han, Antonio Giordano, Sarah C. Mutka, Keren Moss, Sam Suzuki, Brian Sullivan, Igor Gorbatchevsky, Barbara Pistilli, for the VIKTORIA-1 Study Group, Rachel M. Layman, Robert Wesolowski, Erica Stringer-Reasor, Rena D. Callahan, Hyo S. Han, William Irvin, Issam Makhoul, Jennifer Specht, Massimo Cristofanilli, Hiba Jabbour, David Chan, Antonio Giordano, Ritesh Parajuli, Andrea Silber, Hema Vankayala, Delia Guaqueta, Tayyaba Bashir, Gerburg Wulf, Ricardo Alvarez, Sibel Blau, Jennifer M. Suga, Sunil G. Babu, Amanda Gillespie-Twardy, Kathryn Elizabeth Hudson, Urszula Sobol, Wederson M. Claudino, Cynthia Osborne, Jose Guimaraes, Danielle Charpentier, Jeffrey Sulpher, Cameron Phillips, Daniel Egle, Martin Wiesholzer, Renate Pusch, Sonja Heibl, Laure Nuytemans, Francois Duhoux, Patrick Neven, Sevilay Altıntaş, Nicolás Isambert, Barbara Pistilli, Marie Meurer, Mónica Arnedos, Youssef Tazi, Frank Priou, George Emile, Christoph Mundhenke, Marcus Schmidt, M. Hackenthal, Toralf Reimer, Mustafa Deryal, Joke Tio, Marina Cazzaniga, Giuseppe Tonini, Marco Angelo Colleoni, Giampaolo Tortora, Laura Biganzoli, Daniela Boggiani, Y. Izarzugaza Perón, Alba Gonzalez-Haba Martinez, Noelia Martínez Jáñez, Carmela Rodríguez López, José Luis Alonso Romero, Santiago González Santiago, Agostina Stradella Trucco, Cristina Saavedra Serrano, Sarah Khan, Alistair Ring, Ciara O’Brien, Simon Waters, Alistair Ring, Davide Mauri, Grigorios Rallis, Kostantinos Papazisis, Flora Zagouri, Rossitza Krasteva, Assia Konsoulova, Ivan Donev, Nadezhda Miteva-Yovcheva, Tomáš Büchler, Bohuslav Melichar, Eugen Kubala, Péter Árkosy, Judit Kocsis, Lubomir Bodnar, Ewa E. Kalinka, Boguslawa Karaszewska, Zbigniew Nowecki, Katarzyna Hetman, Aleksandra Grela-Wojewoda, Maciej Studziński, Barbara Radecka, Patricia Visan, Michael Schenker, Aurelia Alexandru, Alina Amalia Herzal, Nicoleta Zenovia Antone, Andrei Ungureanu, Govind K Babu, Hemant Malhotra, Louisa L. Lo, Catherine Shannon, Mohammed Islam, Junghoon Shin, Jee Hung Kim, Sung-Bae Kim, Su-Jin Koh, G. Kim, Kyong Hwa Park, Valerie Heong, Terence Alk Huang Tan, Nan Soon Wong, Lynette Ngo Su-Mien, Liang-Chih Liu, Ling-Ming Tseng, Ming‐Feng Hou, Shou-Tung Chen, Yen‐Shen Lu, Kuo-Ting Lee, Jo‐Pai Chen, Ernesto Korbenfeld, Guillermo Streich, Geronimo Rosselli, Juan Manuel Puig, Susana Kahl, Juan Jose Rodriguez, Martin Eduardo Richardet, Cristian Micheri, Matias Salazar, Jorge Nadal, María Marta Bader, M.L. Casalnuovo, Laura Testa, Giuliano Santos Borges, Marcelle Goldner Cesca, Fábio Franke, Graziela Zibetti Dal Molin, Virginia Moreira Braga, Bruno Melo Fernandes, Marlid Cruz, Ivan Martinez Alvarez, Daniel Motola, Cynthia Villarreal, Mario Solares Sánchez, Eva Willars Inman, Yuly A. Remolina-Bonilla, J. Martinez Rodriguez · 发表于：Journal of Clinical Oncology · 年份：2026 · DOI：10.1200/jco-25-02643 · 被引用次数：8 · 研究领域：Advanced Breast Cancer Therapies、PI3K/AKT/mTOR signaling in cancer、Cancer-related Molecular Pathways

PURPOSE Gedatolisib potently targets all four class I PI3K isoforms and mTORC1 and mTORC2 to comprehensively block the PI3K/AKT/mTOR pathway and has shown compelling activity in early clinical trials with palbociclib and fulvestrant. METHODS This phase III randomized trial (VIKTORIA-1; ClinicalTrials.gov identifier: NCT05501886 ) evaluated the efficacy of gedatolisib-based therapy, comparing gedatolisib, palbociclib, and fulvestrant (gedatolisib triplet) and gedatolisib plus fulvestrant (gedatolisib doublet) with fulvestrant monotherapy in patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative (HER2−), PIK3CA wild-type (WT) advanced breast cancer. Eligible patients had disease progression during or after CDK4/6 inhibitor and aromatase inhibitor treatment. Comparison of progression-free survival as assessed by blinded independent central review for gedatolisib triplet versus fulvestrant and gedatolisib doublet versus fulvestrant was the primary objective. RESULTS A total of 392 patients were randomly assigned 1:1:1. The median study follow-up was 10.1 months. The median progression-free survival was 9.3 months in the gedatolisib-triplet group, 2.0 months in the fulvestrant group (hazard ratio [HR] for progression or death, 0.24 [95% CI, 0.17 to 0.35]; P < .001), and 7.4 months in the gedatolisib-doublet group (HR, 0.33 [95% CI, 0.24 to 0.48]; P < .001 v fulvestrant). Grade ≥3 treatment-related adverse events (TRAEs) reported in the gedatolis...