EU Approves Datroway for Triple-Negative Breast Cancer: First-Line Treatment Shifts from Chemotherapy Toward Precision Delivery

Metastatic triple-negative breast cancer lacks common therapeutic targets such as hormone receptors and HER2. If patients are also unsuitable for immunotherapy, first-line options have long relied primarily on chemotherapy. The European Commission has now approved Datroway (datopotamab deruxtecan) for this group of adult patients, formally bringing the use of TROP2 on the tumor surface for precision drug delivery from clinical trials into European treatment settings.

The approval applies to unresectable or metastatic triple-negative breast cancer that is unsuitable for treatment with PD-1/PD-L1 inhibitors, with Datroway used as first-line monotherapy. Reasons for being unsuitable for immunotherapy may include a lack of the relevant tumor biomarkers, prior use of immunotherapy during an earlier treatment stage, limitations due to comorbidities, or lack of access to treatment in the patient’s region. The approval therefore covers a population with a clear clinical need, but does not apply to all patients with triple-negative breast cancer.

Datroway is an antibody-drug conjugate: the antibody recognizes TROP2, which is found on the surface of various solid tumors, and carries the topoisomerase I inhibitor DXd through a cleavable linker, with the aim of delivering the cytotoxic drug more selectively into tumors. This design does not mean that systemic toxicity is absent, but it changes how the drug reaches cancer cells and advances antibody-drug conjugates into first-line treatment for triple-negative breast cancer.

The approval is based on the international Phase 3 TROPION-Breast02 trial. The study randomly assigned 644 patients who had not received treatment for advanced disease in a 1:1 ratio to Datroway, with 323 patients, or investigator’s choice of chemotherapy, with 321 patients. Chemotherapy options included paclitaxel, nab-paclitaxel, carboplatin, capecitabine, or eribulin. The trial used an open-label design, but progression-free survival was assessed by blinded independent central review and was a primary endpoint alongside overall survival.

The results showed that median progression-free survival was 10.8 months in the Datroway group and 5.6 months in the chemotherapy group, with a hazard ratio for disease progression or death of 0.57. Median overall survival was 23.7 and 18.7 months, respectively, with a hazard ratio of 0.79; in other words, the medians differed by five months. These figures reflect statistical results at the population level and cannot directly predict how much an individual patient’s survival may be extended.

The improvement in efficacy was also accompanied by toxicities requiring management. Grade 3 or higher treatment-related adverse events occurred in 33% of patients in the Datroway group and 29% in the chemotherapy group. Treatment discontinuation due to treatment-related adverse events occurred in 4% and 7%, respectively, and there were no treatment-related deaths in either group. The overall safety profile was consistent with previous studies of the drug, but the open-label design, variation in the chemotherapy comparator regimens, and the trial’s inclusion only of patients unsuitable for immunotherapy all limit the extent to which the results can be extrapolated to other patient populations.

The EU approval establishes a new option for a specific patient population, rather than broadly replacing chemotherapy or immunotherapy. Whether Datroway enters widespread clinical use will also depend on pricing, reimbursement, and healthcare system decisions in each member state. Long-term safety, real-world effectiveness, and how subsequent treatments are sequenced will also determine the extent to which this survival benefit ultimately translates into public health benefits.