Tumor Treating Fields With Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: Randomized, Open-Label, Pivotal Phase III PANOVA-3 Study

作者：Hani M. Babiker, Vincent J. Picozzi, Sreenivasa R Chandana, Bohuslav Melichar, Anup Kasi, Jin Gang, Javier Gallego, Andrea Bullock, Hao Chunyi, Lucjan Wyrwicz, Erika Hitre, Arsen Osipov, Christelle de la Fouchardière, Inmaculada Alés, Tomislav Dragovich, Woo Jin Lee, Kynan Feeney, Philip A. Philip, Makoto Ueno, Eric Van Cutsem, Thomas Seufferlein, Teresa Macarulla, on behalf of the PANOVA-3 Study Investigators, David R. Spigel, Arsen Osipov, Marc Matrana, Nicholas Blondin, Emil Lou, Rachna T. Shroff, Douglas Orr, Michael J. Anderson, Anthony F. Shields, John Hamm, Andrea Bullock, Sumana Nagireddy, Joanna Kolodney, Tomislav Dragovich, Andrew L. Coveler, Ajit Maniam, Vincent J. Picozzi, Judith D. Sears, Joseph Stilwill, Francis P. Arena, Mike Cusnir, Anna Niewiaroska, William Small, Anup Kasi, Jason Tache, Sharona Ross, Samer Shihabi, Sunil Gandhi, J. N. Reeves, Garrett Green, Trevor Feinstein, Timothy K. Huyck, Nadia Ramdin, Robert Marsh, Yixing Jiang, Hassan Hatoum, Sudhir Manda, Mark D. Kochenderfer, Henrik Illum, Donald Richards, P. Valilis, Lucas Wong, Sreenivasa R Chandana, Herbert B. Newton, Maen Abdelrahim, David Einspahr, Richard Siegel, Scott McKenney, Mohit Narang, Marc Uemura, Higinia R. Cárdenes, Kannan Thanikachalam, Joshua P. Raff, Joseph Ye, Deepti Behl, Audrey E. Kam, Paul DeRose, A. Tasneem, Warren Brenner, Jennifer De Los Santos, James Z. Wang, D C Rausch, Gaurav Trikha, Jae‐Hyun Park, Nashat Gabrail, Rex B. Mowat, Khawaja Jahangir, Robert P. Schumaker, Edward Soffen, Eric Bravin, Mukul Kumar Gupta, Hani M. Babiker, Ivan Dario Bedoya-Apraez, Tyler Y. Kang, Frédéric Lemay, Mark Vincent, Richard Létourneau, Martin Fuchs, Thomas Seufferlein, Christine Doehring, Mike Haberkorn, Arndt Vogel, Karen Rußwurm, Jack Chater, Marc Küng, Sabine Schacher, Maria Passhak, Ravit Geva, Ayala Hubert, Salomon M. Stemmer, Talia Golan, Hélène Senellart, Isabelle Trouilloud, Christelle de la Fouchardière, Jean-Frederic Blan, Luis-Marie Dourthe, Florence Le Roy, J. Martin-Babau, Méher Ben Abdelghani, Richard Greil, Georg Schreil, Armin Gerger, Wolfgang Eisterer, T. Macarulla Mercadé, Antonio Cubillo, Francesc Valladares Pons, Carmen Guillén‐Ponce, Inmaculada Alés Díaz, Fernando Rivera, Javier Gállego, Ricardo Yayá, Mariano Ponz Sarvise, Bruno Vincenzi, Mario Airoldi, Giovanna Bellotti, Domenico Corsi, Lorenzo Antonuzzo, Bohuslav Melichar, Petra Holečková, Luboš Petruželka, Rostislav Kotasek, Radim Němeček, Eric van Cutsem, Jean‐Luc Van Laethem, Ivan Borbath, Jun‐Eul Hwang, Sung Yong Oh, Sun Jin Sym, Moon Hee Lee, Jin Young Kim, Sang Cheul Oh, Woo Jin Lee, Joon Oh Park, Jin Won Kim, Myung Ah Lee, Hye Jin Choi, Seok Yun Kang, Hong Jae Chon, Lucjan Wyrwicz, Rodryg Ramlau, Andrzej Mruk, Beata Freier, Ewa Anna Kosakowska, Judit Kocsis, Tibor Csőszi, Erika Hitre, Yousuf Al-Farhat, A. Bassam, Chunyi Hao, Bo Liang, Shundong Cang, Gang Jin, Changzeng Zuo, Lijie Song, Zheng Wu, Jie Gao, Tao� Zhang, Yusheng Wang, Xin Yuan, Zhi-Hua Li, Rufu Chen, Wei Li, Xiujun Cai, Zhizhen Zhu, Yuxian Bai, Chunmei Bai, Thomas Yau, Warren Joubert, Ka Yeung Mark Wong, Gavin Marx, Kynan Feeney, Marion Harris, Ana Mišir, Adilson Faccio, Felipe Melo Cruz, Srergio De Azevedo, Ana Paula Victorino, Tadeu Ferreira Paiva, Fábio Franke, Katsuki Arima Tiscoski, Gabriel Parolla, Flora Lilno, Mariana Bruno Siqueira, Marcos Lyra, Paulo M. Hoff, Jose Luis Martinez Lira, Dolores Mendoza Oliva, Arturo Vazquez, Jesus Elvis Cabrera Luviano, Erika Castillo Gutiérrez, Vanessa Rosas Camargo, Cristian Chavez Guerra, Osvaldo Hernandez Flores, David Cortez, Saúl Campos-Gómez, Iván Romarico González Espinoza, Jessica Reyes Contreras, Ángel Gómez Villanueva, Omar Zayas Villanueva · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco-25-00746 · 被引用次数：44 · 研究领域：Microbial Inactivation Methods、Pancreatic and Hepatic Oncology Research、Cancer Research and Treatments

PURPOSE Tumor treating fields (TTFields) use alternating electric fields to disrupt cancer cell proliferation. Feasibility of TTFields therapy with gemcitabine/nab-paclitaxel was previously demonstrated in patients with advanced pancreatic adenocarcinoma. PANOVA-3 was designed to confirm safety and efficacy of TTFields in patients with unresectable locally advanced pancreatic adenocarcinoma (LA-PAC). METHODS In this global phase III trial, 571 patients with newly diagnosed LA-PAC were randomly assigned to receive gemcitabine 1,000 mg/m 2 and nab-paclitaxel 125 mg/m 2 by intravenous infusion once a day on days 1, 8, and 15 of a 28-day cycle with or without TTFields. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), local PFS, pain-free survival, and overall response rate (ORR). Distant PFS was analyzed post hoc. RESULTS OS was significantly prolonged using TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel (median, 16.2 months [95% CI, 15.0 to 18.0] v 14.2 months [95% CI, 12.8 to 15.4]; hazard ratio [HR], 0.82 [95% CI, 0.68 to 0.99]; P = .039). PFS, local PFS, and ORR were not improved. Pain-free survival was significantly prolonged with TTFields with gemcitabine/nab-paclitaxel (median, 15.2 months [95% CI, 10.3 to 22.8] v 9.1 months [95% CI, 7.4 to 12.7]; HR, 0.74 [95% CI, 0.56 to 0.97]; P = .027), as was distant PFS (median, 13.9 months [95% CI, 12.2 to 16.8] v 11.5 months [95% CI, 10.4 to ...