Dr Callahan on the FDA Approval of Dato-DXd for Unresectable or Metastatic TNBC

“If a patient recurs 1 year or 9 months after [prior lines of chemotherapy and immunotherapy], we’re not going to be inclined to give them the same chemotherapy or similar chemotherapy again. We want a different option, and Dato-DXd presents us with that option.”

Rena D. Callahan, MD, a breast medical oncologist at UCLA Health and an associate clinical professor of medicine at the David Geffen School of Medicine at UCLA, highlighted the significance of the FDA approval of datopotamab deruxtecan-dlnk (Datroway; Dato-DXd) in the unresectable or metastatic triple-negative breast cancer (TNBC) treatment paradigm.

On May 22, 2026, the FDA approved Dato-DXd for the treatment of adult patients with unresectable or metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitor therapy. This regulatory decision was backed by data from the phase 3 TROPION-Breast02 trial (NCT05374512), in which Dato-DXd elicited a median overall survival (OS) of 23.7 months vs 18.7 months with chemotherapy (HR, 0.79; 95% CI, 0.64-0.98; P = .0290).

Callahan emphasized that although patients with HER2-positive and hormone receptor–positive metastatic breast cancer often achieve OS durations reaching approximately 6 years, such longevity remains a rarity for patients with TNBC. Consequently, the integration of additional therapies, particularly antibody-drug conjugates (ADCs), has become a high priority for the TNBC field, she said.

Callahan noted that ADCs such as Dato-DXd are advantageous because they generally exhibit fewer or more distinct toxicities compared with standard chemotherapy regimens. Furthermore, clinical data indicated that Dato-DXd demonstrates superior efficacy compared with standard agents and maintained a safety profile with no new or unexpected signals.

However, Callahan noted that the transition to using Dato-DXd in TNBC clinical practice requires a dedicated focus on provider and nursing education due to its unique adverse effect profile. She explained that managing these toxicities involves a learning curve for the medical team, particularly regarding ophthalmologic toxicities. Clinical protocols for Dato-DXd use must involve collaboration with optometrists or ophthalmologists, as patients are required to use specific eye drops and attend regular specialty visits. Additionally, cases of stomatitis may need to be managed. Despite these requirements, Callahan concluded that these toxicities are manageable for most patients, many of whom are eager to receive the therapy.