Datopotamab deruxtecan in patients with untreated, advanced triple-negative breast cancer (TROPION-Breast02): a randomised, open-label, international, phase III trial

Author(s): R. Dent1; Z. Shao2; P. Schmid3; J. Cortes4; D.W. Cescon5; S. Saji6; K.H. Jung7; T. Bachelot8; S. Wang9; E.M. Ramírez10; G. Basaran11; A. Stradella12; R. Mathiba13; S.-C. Chen14; K. Shen15; Á. Wéber16; N. Battelli17; N. Niikura18; T. Luo19; Y.S. Chae20; N. Fischbach21; G. Garbaos22; A. Patera23; K. Zhao24; P. Vuković25; M.J. Maxwell26; T. Traina27;
Source: DOI: 10.1016/j.annonc.2026.03.008
Original Article
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644 patients who are triple-negative breast cancer (TNBC) not candidates for immunotherapy were randomly assigned to receive Dato-DXd (n = 323) or chemotherapy (n = 321). Median progression-free survival (PFS) was 10.8 months with Dato-DXd and 5.6 months with chemotherapy. Median overall survival (OS) was 23.7 months and 18.7 months with Dato-DXd and chemotherapy, respectively HR 0.79; P = 0.029]. Treatment-related adverse events (TRAEs) of grade ≥3 were reported in 105 (33%) and 89 (29%) patients who received Dato-DXd and chemotherapy, respectively, they were more treatment discontinuation in the chemotherapy arm secondary to treatment related adverse events in 14 (4%) and 23 (7%) patients. There were no treatment-related deaths in either arm. New standard of care? Recall this is on patients not eligible for immunotherapy.

ABSTRACT

Highlights•In TROPION-Breast02, Dato-DXd demonstrated statistically significantly improved PFS by BICR and OS versus chemotherapy.•Confirmed ORR was higher and median DoR was longer with Dato-DXd than with chemotherapy.•The safety profile of Dato-DXd was consistent with that reported in previous studies.•Rates of serious and grade ≥3 TRAEs were similar, and discontinuation due to TRAEs was lower with Dato-DXd versus chemotherapy.AbstractBackgroundPrognosis is poor, and treatment options are limited for patients with previously untreated, advanced triple-negative breast cancer (TNBC), especially for those who are not candidates for immunotherapy.Patients and methodsIn the randomised, open-label, phase III TROPION-Breast02 trial, patients with previously untreated, locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option were randomly assigned 1:1 to datopotamab deruxtecan (Dato-DXd; 6 mg/kg intravenously every 3 weeks) or investigator’s choice of chemotherapy. Randomisation was stratified by geographic location, disease-free interval, and programmed cell death ligand-1 status. Dual primary endpoints were progression-free survival (PFS; blinded independent central review per RECIST version 1.1) and overall survival (OS). Efficacy analyses were performed in the intention-to-treat population. Safety analyses included all patients who received ≥1 dose of study treatment.ResultsBetween 16 May 2022 and 11 June 2024, 644 patients were randomly assigned to receive Dato-DXd (n = 323) or chemotherapy (n = 321). Median PFS was 10.8 months [95% confidence interval (CI) 8.6-13.0] with Dato-DXd and 5.6 months (95% CI 5.0-7.0) with chemotherapy [hazard ratio 0.57 (99% CI 0.44-0.73); P < 0.0001]. Median OS was 23.7 months (95% CI 19.8-25.6) and 18.7 months (95% CI 16.0-21.8) with Dato-DXd and chemotherapy, respectively [hazard ratio 0.79 (95.01% CI 0.64-0.98); P = 0.029]. Treatment-related adverse events (TRAEs) of grade ≥3 were reported in 105 (33%) and 89 (29%) patients who received Dato-DXd and chemotherapy, respectively, and TRAEs led to treatment discontinuation in 14 (4%) and 23 (7%) patients. There were no treatment-related deaths in either arm.ConclusionsDato-DXd demonstrated significantly improved PFS and OS versus chemotherapy in patients with previously untreated, locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option. Safety was consistent with the known profile for Dato-DXd.Graphical abstract

Author Affiliations

1Department of Medical Oncology, National Cancer Center Singapore, Singapore and Duke-NUS Medical School, Singapore, Singapore; 2Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; 3Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London, UK; 4International Breast Cancer Center (IBCC), Pangaea Oncology, Barcelona and IOB Madrid, Institute of Oncology, Madrid, Spain; 5Department of Medical Oncology, Princess Margaret Cancer Centre/UHN, Toronto, Canada; 6Department of Medical Oncology, Fukushima Medical University, Fukushima, Japan; 7Department of Oncology, Asan Medical Center – University of Ulsan College of Medicine, Seoul, Republic of Korea; 8Medical Oncology Department, Centre Léon Bérard, Lyon, France; 9Department of Breast Surgery, Xiangya Hospital of Central South University, Changsha, China; 10Centro Médico Nacional de Occidente, Zapopan, Mexico; 11Medical Oncology Department, MAA Acıbadem University, School of Medicine, Istanbul, Türkiye; 12Department of Medical Oncology, Institut Catala d'Oncologia – Hospitalet – IDIBELL, Barcelona, Spain; 13Medical Oncology Department, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa; 14Division of Breast Surgery, Chang Gung Medical Foundation – Taipei Chang Gung Memorial Hospital, Taipei City, Taiwan; 15Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 16Szabolcs-Szatmár-Bereg County Teaching Hospital, Nyíregyháza, Hungary; 17Oncology Unit, Ospedale Generale Provinciale Macerata, Macerata, Italy; 18Department of Breast Oncology, Tokai University School of Medicine, Kanagawa, Japan; 19West China Hospital, Sichuan University, Chengdu, China; 20Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, Kyungpook National University School of Medicine, Kyungpook, Republic of Korea; 21Department of Oncology, Yale University School of Medicine, New Haven, USA; 22Instituto Médico de la Fundación Estudios Clínicos, Santa Fe, Argentina; 23Global Patient Safety, Oncology R&D, AstraZeneca, Gaithersburg, USA; 24Biometrics, Late-Stage Development, Oncology R&D, AstraZeneca, Wilmington, USA; 25Clinical Development, Late-Stage Development, Oncology R&D, AstraZeneca, Cambridge, UK; 26Clinical Development, Late-Stage Development, Oncology R&D, AstraZeneca, Gaithersburg, USA; 27Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA

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