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