Datopotamab Deruxtecan Versus Chemotherapy in Previously Treated Inoperable/Metastatic Hormone Receptor–Positive Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer: Primary Results From TROPION-Breast01
Authors: Aditya Bardia, Komal Jhaveri, Seock-Ah Im, Sonia Pernas, Michelino De Laurentiis, Shusen Wang, Noelia Martínez Jañez, Giuliano Borges, David W. Cescon, Masaya Hattori, Yen-Shen Lu, Erika Hamilton, Qingyuan Zhang, Junji Tsurutani, Kevin Kalinsky, Pedro Emanuel Rubini Liedke, Lu Xu, Rick M. Fairhurst, Sabrina Khan, Neelima Denduluri, Hope S. Rugo, Binghe Xu, Barbara Pistilli, Betiana Romitelli, Ernesto Korbenfeld, Cristian Buono, Arturo Barbero, Geronimo Rosselli, Sergio Daniele, Sandra Anabel Ostoich, Hans Wildiers, Kevin Punie, Joëlle Collignon, Guy Jerusalem, Andrea Gombos, Giuliano Borges, Pedro Emanuel Rubini Liedke, Marcelle Cesca, Patricia Beato, Laura Testa, Helio Pinczowski, Liane Rapatoni, Debora Jardim, José Bines, David W. Cescon, Jamil Asselah, Andre Blais, Joanne Yu, Jennifer Friedmann, Cristiano Ferrario, Binghe Xu, Shusen Wang, Qingyuan Zhang, ZeFei Jiang, Zhongsheng Tong, Quchang Ouyang, Jingfen Wang, Tingjing Yao, Yongsheng Wang, Xiaojia Wang, Meili Sun, Hui Li, Shu Wang, Yuan Sheng, Aimin Zang, Zhanmin Zhang, Wenyan Chen, Xian Wang, Zhong Ouyang, Wei Li, Barbara Pistilli, Thomas Bachelot, Mony Ung, Cristian Villanueva, Delphine Garbay, Anne-Claire Hardy-Bessard, Audrey Mailliez, Stéphanie Becourt, William Mina, Thomas Decker, Julia Radosa, Andreas Schneeweiß, Michael Braun, Bahriye Aktas, Gábor Rubovszky, Zsuzsanna Pápai, Tibor Csőszi, Yousuf Al-Farhat, Ankit Patel, Vineet Gupta, Richu Sharma, Chandrakanth Mosale Venkatesha, Shailesh Bondarde, Somnath Roy, Nikhil Ghadyalpatil, Lalit Sharma, Rajani Yedla, Michelino De Laurentiis, Ida Paris, Claudio Zamagni, Valentina Guarneri, Icro Meattini, Marco Colleoni, Giampaolo Bianchini, Ugo De Giorgi, Filippo Montemurro, Elena Geuna, Laura Biganzoli, Junji Tsurutani, Masaya Hattori, Yukinori Ozaki, Akihiko Shimomura, Naoki Niikura, Mitsuya Itoh, Tetsuhiko Taira, Toru Mukohara, Kenjiro Aogi, Tsutomu Iwasa, Eriko Tokunaga, Shigehira Saji, Nobuko Kawaguchi, Toshinari Yamashita, Kenichi Inoue, Takahiro Nakayama, Kenichi Watanabe, Masayuki Nagahashi, Kan Yonemori, Jan Drooger, Inge Konings, Agnès van de Wouw, Zbigniew Nowecki, Ewa Chmielowska, Iwona Danielewicz, Jacek Jassem, Ewa Kalinka, Bogumiła Czartoryska-Arłukowicz, Bogusława Karaszewska, Mariusz Kwiatkowski, Seock-Ah Im, Joo Hyuk Sohn, Yeon Hee Park, Keun Seok Lee, Kyung Hae Jung, Kyong Hwa Park, Jee Hung Kim, Daniil Stroyakovskiy, Elena Artamonova, Martha Mekebeb-Reuter, Bernardo Rapoport, Elizabeth Schoeman, Maria Coccia-Portugal, Rofhiwa Mathiba, Sonia Pernas, Noelia Martínez Jañez, Barbara Adamo, Begoña Bermejo de las Heras, José Ángel García Sáenz, Manuel Ruiz Borrego, María Emilia Domínguez, Begoña Jiménez Rodríguez, Silvia Antolín Novoa, Elena Galve Calvo, Javier Cortés Castán, Juan Lucas Bayo Calero, Shin-Cheh Chen, Ling-Ming Tseng, Yen-Shen Lu, Wei-Pang Chung, Yuan-Ching Chang, Chien-Ting Liu, Hwei-Chung Wang, Kun-Ming Rau, Charles Comins, Jeremy Braybrooke, Annabel Borley, Ciara O'Brien, Caroline Michie, Peter Schmid, Sophie McGrath, Duncan Wheatley, Mukesh Mukesh, Sachin Trivedi, Syed Karim, Pavel Bezecny, Aditya Bardia, Hope S. Rugo, Kevin Kalinsky, Erika Hamilton, Komal Jhaveri, Yuan Yuan, Niki Patel, Joanne Mortimer, Sara Tolaney, Amy Vander Woude, Gail Wright, Fauzia Riaz, Apurva Pandey, Halle Moore, Masey Ross, Kelly McCann
Journal: Journal of Clinical Oncology (2024)

PURPOSE The global, phase 3, open-label, randomized TROPION-Breast01 study assessed the trophoblast cell surface antigen 2–directed antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) versus investigator's choice of chemotherapy (ICC) in hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) breast cancer. METHODS Adult patients with inoperable/metastatic HR+/HER2‒ breast cancer, who had disease progression on endocrine therapy, for whom endocrine therapy was unsuitable, and had received one to two previous lines of chemotherapy in the inoperable/metastatic setting, were randomly assigned 1:1 to Dato-DXd (6 mg/kg once every 3 weeks) or ICC (eribulin/vinorelbine/capecitabine/gemcitabine). Dual primary end points were progression-free survival (PFS) by blinded independent central review (BICR) and overall survival (OS). RESULTS Patients were randomly assigned to Dato-DXd (n = 365) or ICC (n = 367). Dato-DXd significantly reduced the risk of progression or death versus ICC (PFS by BICR hazard ratio [HR], 0.63 [95% CI, 0.52 to 0.76]; P &lt; .0001). Consistent PFS benefit was observed across subgroups. Although OS data were not mature, a trend favoring Dato-DXd was observed (HR, 0.84 [95% CI, 0.62 to 1.14]). The rate of grade ≥3 treatment-related adverse events (TRAEs) with Dato-DXd was lower than ICC (20.8% v 44.7%). The most common TRAEs (any grade; grade ≥3) were nausea (51.1%; 1.4%) and stomatitis (50%; 6.4%) with Dato-DXd and neutropenia (grouped term, 42.5%; 30.8%) with ICC. CONCLUSION Patients receiving Dato-DXd had statistically significant and clinically meaningful improvement in PFS and a favorable and manageable safety profile, compared with ICC. Results support Dato-DXd as a novel treatment option for patients with inoperable/metastatic HR+/HER2‒ breast cancer who have received one to two previous lines of chemotherapy in this setting.