Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer

作者：David W. Miles, Joseph Gligorov, Fabrice André, David Cameron, Andreas Schneeweiß, Carlos H. Barrios, Binghe Xu, Andrew M. Wardley, Diego Lucas Kaen, Livia Andrade, Владимир Федорович Семиглазов, Mattea Reinisch, Shilpen Patel, Monika Patre, Lucas G. Morales, Sipahee Lal Patel, Manika Kaul, Teresa Barata, Joyce A O'Shaughnessy, Q. Zhang, Binghe Xu, Zhimin Shao, Xiangyu Wang, Cuizhi Geng, Xingchen Yan, Zhongsheng Tong, Kunwei Shen, Yongmei Yin, Tao Sun, J. Yang, Jianting Feng, Min Yan, Yan Wang, Qiang Liu, S. Zhang, Michelino De Laurentiis, Armando Santoro, Valentina Guarneri, Marco Angelo Colleoni, Clara Natoli, Laura Cortesi, Sabino De Placido, Lorenzo Gianni, Francesco Ferraù, Lorenzo Livi, Alberto Zambelli, Lucia Del Mastro, Giuseppe Tonini, Filippo Montemurro, Giulia Bianchi, R. Pedersini, Salvatore A. Del Prete, Giacomo Allegrini, Giuseppe Naso, Patrizia Vici, Delphine Loirat, Audrey Mailliez, Franck Priou, Olivier Trédan, F. Dalenc, Christophe Perrin, Joseph Gligorov, Morales-Pancorbo David, Nadine Dohollou, Luís Teixeira, Fabien Brocard, Antoine Arnaud, Suzette Delaloge, Jean‐Philippe Spano, Luigi Mansi, Livia Andrade, Fernanda Damian, José Luiz Pedrini, Sandra M. Aleixo, Roberto Hegg, R. Junior, Mattea Reinisch, Marcus Schmidt, Chantal-Kristin Wenzel, E.‐M. Grischke, Andreas Schneeweiß, Marianne Just, Nadia Harbeck, Claudia Schumacher, Ubong Peters, Dorothea Fischer, Helmut Forstbauer, Rüdiger Liersch, Ellen Warner, Nathaniel Bouganim, C. T. Doyle, Julie Price Hiller, Ted A. Vandenberg, Michel Pavic, Andrew George Robinson, Gloria Roldan Urgoiti, Nadia Califaretti, Ahmet Alacacıoğlu, M. Gumus, Bülent Yalçın, I. Cicin, Fatih Köse, Kazım Uygun, Kaplan Ma, Erdem Çubukçu, Andrew M. Wardley, Mark Harries, David W. Miles, Dinesh Doval, Sameer Gupta, Prerana Mohapatra, Sanjoy Chatterjee, Nikhil Suresh Ghadyalpatil, Manish Kumar Singhal, S. Nag, Amit Agarwal, Ido Wolf, Einav Gal Yam, Rinat Yerushalmi, Tamar Peretz, Georgeta Fried, Noa Ben Baruch, Deborah Ann Katz, E.P. Hamilton, Fadi Kayali, Adam Brufsky, Melinda L. Telli, Gail Shaw Wright, Raul H. Oyola, Thomas J. Rakowski, Stephanie L. Graff, Sergei Tjulandin, Владимир Федорович Семиглазов, Ana Maria Aparicio, Manuel Ruíz Borrego, Luis de la Cruz‐Merino, Joaquín G. Martínez, Escarlata López, Toshinari Yamashita, Shoichiro Ohtani, Kenichi Inoue, Y. Ito, Naoki Niikura, Takahiro Nakayama, Yasuaki Sagara, Yorihide Yanagita, Yuhei Kamada, K. Kaneko, Diego Lucas Kaen, Adrián Nervo, Alexandru E. Eniu, Michael Schenker, Peter Priester, Bohuslav Melichar, Martina Zimovjanová, P. Sormova, Jozef Šufliarský, M. Kakalejcik, Rizlane Belbaraka, Hassan H Errihani, D. Than, D. Pham, Gerasimos Aravantinos, CHRISTOS A. PAPADIMITRIOU, Georgios Koumakis, Christos N. Papandreou, Paula Podolski, Keo Tabane · 发表于：Annals of Oncology · 年份：2021 · DOI：10.1016/j.annonc.2021.05.801 · 被引用次数：756 · 研究领域：Cancer Immunotherapy and Biomarkers、Advanced Breast Cancer Therapies、Breast Cancer Treatment Studies

BACKGROUND: In the phase III IMpassion130 trial, combining atezolizumab with first-line nanoparticle albumin-bound-paclitaxel for advanced triple-negative breast cancer (aTNBC) showed a statistically significant progression-free survival (PFS) benefit in the intention-to-treat (ITT) and programmed death-ligand 1 (PD-L1)-positive populations, and a clinically meaningful overall survival (OS) effect in PD-L1-positive aTNBC. The phase III KEYNOTE-355 trial adding pembrolizumab to chemotherapy for aTNBC showed similar PFS effects. IMpassion131 evaluated first-line atezolizumab-paclitaxel in aTNBC. PATIENTS AND METHODS: (days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status, prior taxane, liver metastases and geographical region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1-positive [immune cell expression ≥1%, VENTANA PD-L1 (SP142) assay] population, and then in the ITT population. OS was a secondary endpoint. RESULTS: Of 651 randomised patients, 45% had PD-L1-positive aTNBC. At the primary PFS analysis, adding atezolizumab to paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.60-1.12; P = 0.20; median PFS 6.0 months with atezolizumab-paclitaxel versus 5.7 months with placebo-paclitaxel]. In the PD-L1-positive population, atezolizumab-paclitaxel was associated with mor...