Global trial shows novel treatment for triple-negative breast cancer nearly doubles survival

• Results of a global, multicentre, phase III clinical trial indicate that datopotamab deruxtecan (Dato-DXd) is effective in improving survival for untreated, advanced triple negative breast cancer (TNBC) 
• TNBC is an aggressive form of breast cancer, for which the majority of patients with previously untreated advanced disease are largely ineligible for immunotherapy (70%) and face poor prognosis

Singapore, 15 April 2026 – A global, multicentre phase III trial, TROPION-Breast02, led by a senior medical oncologist and researcher from the National Cancer Centre Singapore, has demonstrated a significant breakthrough in improving the survival of patients with untreated, advanced triple negative breast cancer (TNBC) using the novel antibody-drug conjugate (ADC) datopotamab deruxtecan (Dato-DXd). Published in the Annals of Oncology on 3 April 2026, the findings demonstrate the potential of Dato-DXd as an effective new treatment option for this aggressive disease.

"In the TROPION-Breast02 trial, first-line Dato-DXd demonstrated clinically meaningful and significant improvements in progression-free survival and overall survival for these TNBC patients, and a higher overall response rate compared with chemotherapy. As a medical oncologist treating triple-negative breast cancer patients for the past 20 years, I am deeply encouraged that this data shows we now have a much-needed new tool to help women affected by this devastating disease,” said lead investigator Prof Rebecca Dent, Deputy CEO (Clinical) and Senior Consultant in the Division of Medical Oncology at the National Cancer Centre Singapore.

The burden of triple negative breast cancer (TNBC)

Breast cancer is the leading cause of cancer death in women globally. Approximately 10 to 20% of breast cancers are TNBC, an aggressive subtype that disproportionately affects young women under the age of 40. TNBC is associated with early recurrence, high likelihood of metastasis and shorter survival. In recent years, TNBC patients with PD-L1-positive tumours or germline BRCA mutations have been eligible for immunotherapy. However, 70% of TNBC patients are ineligible for immunotherapy and receive first-line chemotherapy treatment, which has modest and limited efficacy. Approximately half of patients with metastatic TNBC do not receive treatment beyond first-line chemotherapy, making it an urgent need to find new treatment options to improve clinical outcomes.

A new treatment for TNBC

To address this need, clinician-investigators from multiple centres around the world conducted the TROPION-Breast02 open-label, phase III clinical trial using Dato-DXd to treat TNBC. Dato-DXd is an ADC that delivers a potent cancer-killing drug directly to tumour cells by targeting the TROP2 protein. Currently, Dato-DXd is approved for the treatment of patients with unresectable or metastatic, hormone receptor-positive, HER2-negative breast cancer, but not TNBC.

In total, 644 TNBC patients were enrolled in TROPION-Breast02 across multiple sites across the globe including the United States, Canada, Europe, China, Korea, Japan and Singapore. Patients were randomly assigned to two treatment arms: intravenous Dato-DXd 6 mg/kg once every three weeks (323 patients) or the investigator’s choice of chemotherapy (321 patients). Patients had to be 18 and above to enrol, have locally recurrent inoperable or metastatic TNBC that was untreated, and be ineligible for treatment with immunotherapy.

Trial results showed that:

• Progression-free survival (PFS) was significantly longer with Dato-DXd compared with chemotherapy: median PFS 10.8 months versus 5.6 months (nearly double) 
• Overall survival (OS) was improved with Dato-DXd compared with chemotherapy: median OS 23.7 months versus 18.7 months 
• Patients treated with Dato-DXd had an overall positive response rate to treatment of 63% compared to patients treated with chemotherapy who had an overall response rate of 29%. Median duration of response, or how long patients responded to treatment, was 12.3 months in the Dato-DXd arm and 7.1 months in the chemotherapy arm.

Dato-DXd's most common drug-related adverse events were stomatitis (inflammation of tissue lining the mouth or lips), nausea, alopecia and neutropenia (lower levels of a type of white blood cell), whilst the most common for chemotherapy were alopecia, neutropenia and fatigue. Only 4% of patients on Dato-DXd stopped treatment due to drug-related adverse events compared to 7% of patients on chemotherapy.

What this means for TNBC patients

Not only did the trial find Dato-DXd to be an effective treatment for untreated, inoperable metastatic TNBC, but ASCENT-03, a separate, earlier phase III clinical trial of TROP2-directed ADC sacituzumab govitecan, also demonstrated improved PFS compared to chemotherapy. Combined, the results from TROPION-Breast02 and ASCENT-03 indicate that TROP2-directed ADCs are a promising class of drugs to treat TNBC.

The team is further evaluating Dato-DXd in phase III clinical trials to treat patients with Stage I-III TNBC with residual invasive disease after neoadjuvant systemic therapy, Stage II-III triple-negative or hormone receptor (HR)-low, HER2-low or -negative breast cancer and metastatic TNBC PD-L1 expressed tumours.

Dato-DXd is currently under review as first-line treatment for unresectable, metastatic TNBC by the US Food and Drug Administration and the Singapore Health Sciences Authority.

Study citation:

Dent R, Shao Z, Schmid P, Cortes J, Cescon DW, Saji S, Jung KH, Bachelot T, Wang S, Ramírez EM, Basaran G, Stradella A, Mathiba R, Chen SC, Shen K, Wéber Á, Battelli N, Niikura N, Luo T, Chae YS, Fischbach N, Garbaos G, Patera A, Zhao K, Vuković P, Maxwell MJ, Traina T, on behalf of the TROPION-Breast02 investigators, Datopotamab deruxtecan in patients with untreated, advanced triple-negative breast cancer (TROPION-Breast02): a randomised, open-label, international, phase III trial, Annals of Oncology (2026), doi: https://doi.org/10.1016/j.annonc.2026.03.008.

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For media enquiries, please contact:

Dharshini Subbiah
Corporate Communications
National Cancer Centre Singapore
Email : dharshini.subbiah@nccs.com.sg 

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