Datopotamab Deruxtecan Generates PFS Benefit in Previously Treated HR+/HER2-Low or HER2– Breast Cancer


Datopotamab deruxtecan elicited a statistically significant and clinically meaningful improvement in progression-free survival compared with chemotherapy in patients with inoperable or metastatic hormone receptor–positive, HER2-low or HER2-negative breast cancer.

Ken Takeshita, MD

Ken Takeshita, MD

Datopotamab deruxtecan (DS-1062a) elicited a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with chemotherapy in patients with inoperable or metastatic hormone receptor (HR)–positive, HER2-low or HER2-negative breast cancer who previously received endocrine-based therapy and at least 1 systemic therapy, meeting a coprimary end point of the phase 3 TROPION-Breast01 trial (NCT05104866).1

PFS by blinded independent central review and overall survival (OS) served as coprimary end points for TROPION-Breast01. OS data were immature at the time of the interim analysis, and the trial will continue as planned to evaluate OS. Furthermore, the safety profile of datopotamab deruxtecan was consistent with the safety profiles seen in previous breast cancer clinical trials, and no new safety signals were identified. Additionally, the rates of all-grade interstitial lung disease were low.

Daiichi Sankyo shared that detailed findings from TROPION-Breast01 will be shared at an upcoming medical meeting and submitted to regulatory authorities.

“The positive topline results from TROPION-Breast01 demonstrate the potential for datopotamab deruxtecan to become an important treatment option for patients with HR-positive, HER2-low or -negative breast cancer in the second-line metastatic setting,” Ken Takeshita, MD, global head of research and development at Daiichi Sankyo, said in a press release.

The global, randomized, open-label, multicenter TROPION-Breast01 trial evalauted the safety and efficacy of the antibody-drug conjugate (ADC) datopotamab deruxtecan vs investigator’s choice of single-agent chemotherapy, consisting of capecitabine, eribulin, gemcitabine, or vinorelbine, in 733 patients with metastatic or inoperable HR-positive, HER2-low or -negative breast cancer, defined as immunohistochemistry (IHC) 0, IHC 1+, or IHC 1+/in situ hybridization–negative disease.2 Patients needed to be unsuitable for or have progressed on 1 line of endocrine therapy per investigator assessment. Progression following 1 to 2 lines of prior chemotherapy in the inoperable/metastatic setting was also required. Patients with clinically inactive brain metastases were permitted if they had recovered from radiotherapy-associated acute toxicities.

Patients with history of another primary malignancy not treated with curative intent with no known active disease within 3 years before the first dose of study treatment, as well as those with persistent toxicities caused by previous anticancer therapies, excluding alopecia, were excluded from the trial.

Patients were randomly assigned 1:1 to receive either 100 mg of intravenous (IV) datopotamab deruxtecan or physician’s choice of chemotherapy with oral capecitabine, IV gemcitabine, IV eribulin, or IV vinorelbine.

Key secondary end points included overall response rate, duration of response, investigator-assessed PFS, disease control rate, and time to first subsequent therapy.1

“Today’s TROPION-Breast01 news is a significant development for patients with HR-positive, HER2-low or -negative metastatic breast cancer whose tumors have become insensitive to endocrine therapy and who currently face poor outcomes,” Susan Galbraith, MBBChir, PhD, executive vice president of Oncology Research and Development at AstraZeneca, stated in the press release.

“We look forward to realizing the full potential of this TROP2-directed ADC across breast cancer subtypes through our ongoing phase 3 program, including 2 trials in patients with triple-negative breast cancer,” Takeshita added.


  1. Datopotamab deruxtecandemonstrated statistically significant and clinically meaningful progression-free survival benefit in patients with HR positive, HER2 low or negative breast cancer in TROPION-Breast01 phase 3 trial. News Release. September 22, 2023. Accessed September 22, 2023. https://www.daiichisankyo.com/files/news/pressrelease/pdf/202309/20230922_E.pdf
  2. A phase-3, open-label, randomized study of Dato-DXd versus investigator’s choice of chemotherapy (ICC) in participants with inoperable or metastatic HR-positive, HER2-negatvie breast cancer who have been treated with one or two prior lines of systemic chemotherapy (TROPION-Breast01). ClinicalTrials.gov. Updated July 13, 2023. Accessed September 22, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05104866
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