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
Aditya Bardia, Komal Jhaveri, Seock‐Ah Im, Sònia Pernas, Michelino De Laurentiis, Shusen Wang, Noelia Martínez-Jáñez, 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 S. Khan, Neelima Denduluri, Hope S. Rugo, Binghe Xu, Barbara Pistilli, for the TROPION-Breast01 Investigators, Betiana Romitelli, Ernesto Korbenfeld, Cristian Buono, Arturo Barbero, Geronimo Rosselli, Sergio Daniele, Sandra Anabel Ostoich, Hans Wildiers, Kevin Punie, Joëlle Collignon, Guy Jérusalem, Andrea Gombos, Giuliano Borges, Pedro Emanuel Rubini Liedke, Marcelle Goldner Cesca, Patrícia Medeiros Milhomem Beato, Laura Testa, Hélio Pinczowski, Liane Rapatoni, Debora de Melo Gagliato 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, Zhang Zhanmin, Wenyan Chen, Xian Wang, Zhong Ouyang, Wěi Li, Barbara Pistilli, Thomas Bachelot, Mony Ung, Cristian Villanueva, Delphine Garbay, Anne-Claire Hardy-Bessard, Audrey Mailliez, Stéphanie Bécourt, William Mina, Thomas Decker, Julia Radosa, Andreas Schneeweiß, Michael Braun, Bahriye Aktas, Gábor Rubovszky, Zsuzsanna Pápai, Tibor Csőszi, Yousuf Al-Farhat, Ankit Patel, Vineet Govinda Gupta, Richu Sharma, Chandrakanth Mosale Venkatesha, Shailesh Bondarde, Somnath Roy, Nikhil Ghadyalpatil, Lalit Sen Sharma, Rajani Priya Yedla, Michelino De Laurentiis, Ida Paris
Abstract
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 < .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.