Sustained quality-of-life benefits reported with first-line datopotamab deruxtecan in triple negative breast cancer (ESMO Breast Cancer 2026 Congress)

Immunotherapy is not an option for around 70% of patients with locally recurrent inoperable or metastatic triple negative breast cancer (TNBC) (Oncologist. 2025 Mar 31;30(3):oyaf034 ).

Datopotamab deruxtecan (Dato-DXd) – a trophoblast cell-surface antigen 2 (TROP2)-directed antibody-drug conjugate (ADC) – has recently emerged as an effective first-line monotherapy for these patients, demonstrating to significantly improve progression-free survival (PFS) and overall survival (OS) compared to standard chemotherapy in the phase III TROPION-Breast02 trial (Ann Oncol. 2026 Apr 3:S0923-7534(26)00130-4 ).

Secondary endpoints data from the study, as presented at the ESMO Breast Cancer 2026 congress , also showed sustained improvements in patients’ symptoms, functioning and quality of life (QoL) (Abstract 415O ).

Patient reported outcomes (PROs) were assessed at baseline and throughout the study via electronic PRO questionnaires among the 644 patients involved in the study (n=323 receiving Dato-DXd arm; n=321 receiving chemotherapy by investigator’s choice). Secondary PRO endpoints included time to deterioration (TTD) in global health status (GHS)/QoL, physical functioning and pain using EORTC IL146, and in breast and arm symptoms using EORTC IL116. Exploratory PRO endpoints included TTD and change from baseline in symptoms and functioning using EORTC IL146/116, patient-reported symptomatic adverse events using PRO-CTCAE, EORTC IL147 and Mouth and Throat Symptoms Diary, and patient-reported treatment tolerability using PGI-TT.

Overall, PROs data favoured Dato-DXd compared to chemotherapy, even though patients received the ADC monotherapy for longer (Figure).

Figure. Time to deterioration in GHS/QoL, physical functioning, pain, and breast and arm symptoms was delayed with Dato-DXd versus chemotherapy in TROPION-Breast02 (ESMO Breast Cancer 2026, Abstract 415O)

According to Dr Ines Vaz-Luis from Gustave Roussy Cancer Center, Villejeuf, France, discussing the results during the congress, data presented offer an opportunity to reflect on how to integrate safety and quality of life into clinical decision-making. “Over the last 20 years, dozens of agents have been approved in breast cancer, creating a crowded therapeutic landscape where clinical and reimbursement decisions are increasingly complex,” she said. “So, when we select a drug for a patient, we have to put it in the context of the clinical benefit. Does this drug add time to OS and PFS but also to a better lived time? Does it preserve how patients feel and function? How does it preserve patients' preferences?”

Adverse events reported by patients were generally consistent with clinician-reported safety data which showed that 33% of patients treated with Dato-DXd experienced treatment-related adverse events (TRAEs) of grade ≥3 (33%). “It is important to notice that there is a shift in the adverse events in the Dato-DXd arm compared with those reported in patients receiving chemotherapy,” noticed Vaz-Luis. When comparing Dato-DXd to chemotherapy, in fact, fewer patients reported any abdominal pain, shortness of breath, hair loss, numbness/tingling and general pain, while when comparing chemotherapy to Dato-DXd, fewer patients reported any nausea, vomiting, constipation, fatigue and dry eye.

For Vaz-Luis, these data should encourage medical oncologists to integrate supportive care earlier into the patient journey. “From day one, do eye care, do strong nausea prevention, do rapid triage of respiratory symptoms: this will give our patients a better lived time,” she remarked. “However, average quality of life can hide toxicity patterns that can be important for a specific patient, especially for chronic low-grade symptoms. So, it is important to ask which domains change, which patients deteriorated, and which symptoms are actionable. Having this data is an opportunity to identify actionable domains, trajectories, at-risk clusters, and minimal acceptable benefit for specific toxicities and burden. We need to do a better job at quantifying patient preferences for new therapeutic regimens, and we also need to challenge the instruments that we are using to evaluate the patient experience.”

Source: ESMO Breast Cancer 2026 congress (6 - 8 May, Berlin, Germany) Sustained quality-of-life benefits reported with first-line antibody-drug conjugate in triple negative breast cancer