On January 17, 2025, the Food and Drug Administration (FDA) approved datopotamab deruxtecan-dlnk a Trop-2-directed antibody and topoisomerase inhibitor conjugate. This approval marks a significant advancement in the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer.
The efficacy of datopotamab deruxtecan-dlnk was evaluated in the TROPION-Breast01 trial (NCT05104866), a multicenter, open-label, randomized study. The trial enrolled 732 patients with HR-positive, HER2-negative breast cancer, whose disease had progressed after prior endocrine and chemotherapy treatments. Participants were randomized 1:1 to receive either datopotamab deruxtecan-dlnk (n=365) or the investigator’s choice of chemotherapy (n=367). Chemotherapy options included eribulin (60%), capecitabine (21%), vinorelbine (10%), and gemcitabine (9%).
The primary efficacy outcomes were progression-free survival (PFS), assessed by blinded independent central review (BICR) based on RECIST v1.1, and overall survival (OS). Secondary efficacy outcomes included confirmed objective response rate (ORR) and duration of response (DOR).
The trial demonstrated superior PFS with datopotamab deruxtecan-dlnk compared to standard chemotherapy. Median PFS in the datopotamab deruxtecan-dlnk arm was 6.9 months, compared to 4.9 months in the chemotherapy arm. However, the OS results did not show a statistically significant difference. Median OS was 18.6 month in the datopotamab deruxtecan-dlnk arm and 18.3 months in the chemotherapy arm. The ORR was notably higher in the datopotamab deruxtecan-dlnk arm at 36% compared to 23% in the chemotherapy arm. The median DOR was 6.7 months for datopotamab deruxtecan-dlnk and 5.7 months for chemotherapy.
The approval of datopotamab deruxtecan-dlnk provides a promising new option for patients with HR-positive, HER2-negative breast cancer who have limited treatment alternatives. The improvement in PFS compared to standard chemotherapy underscores its potential as a preferred treatment for this patient population. For healthcare providers, the introduction of datopotamab deruxtecan-dlnk adds to the growing arsenal of targeted therapies for advanced breast cancer. The Trop-2-directed mechanism of action offers a novel approach, addressing a critical gap in the treatment landscape. As more data emerge, the role of datopotamab deruxtecan-dlnk in clinical practice will continue to evolve, potentially reshaping the management of HR-positive, HER2-negative breast cancer.
Sources: Future Oncology, U.S. Food and Drug Administration