DATROWAY: A New Hope for Metastatic HR-Positive, HER2-Negative Breast Cancer

On January 17, 2025, the Food and Drug Administration (FDA) approved datopotamab deruxtecan-dlnk (Datroway, Daiichi Sankyo, Inc.), a Trop-2-directed antibody and topoisomerase inhibitor conjugate, for adult patients with unresectable or metastatic, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC1+ or IHC2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease. This approval marks a significant milestone in the treatment of metastatic breast cancer, offering a new and promising option for patients who have exhausted existing therapies.

The approval of Datroway was based on the results of the TROPION-Breast01 trial, a multicenter, open-label, randomized trial that evaluated the efficacy and safety of Datroway compared to investigator's choice of chemotherapy in patients with unresectable or metastatic HR-positive, HER2-negative breast cancer. The trial enrolled 732 patients who were randomized (1:1) to receive Datroway (n=365) or investigator's choice of chemotherapy (n=367); eribulin (60%), capecitabine (21%), vinorelbine (10%), or gemcitabine (9%).

The major efficacy outcome measures were progression-free survival (PFS), assessed by blinded independent central review (BICR), based on RECIST v1.1 and overall survival (OS). Additional efficacy outcomes included confirmed objective response rate (ORR) and duration of response (DOR) by BICR. Median PFS was 6.9 months (95% CI: 5.7, 7.4) in the Datroway arm and 4.9 months (95% CI: 4.2, 5.5) in the chemotherapy arm (Hazard ratio 0.63 [95% CI: 0.52, 0.76] two-sided p-value <0.0001). Median OS was 18.6 months (95% CI: 17.3, 20.1) in the Datroway arm and 18.3 months (95% CI: 17.3, 20.5) in the chemotherapy arm (Hazard ratio 1.01 [95% CI: 0.83, 1.22]; two-sided p-value was not statistically significant). Confirmed ORR was 36% (95% CI: 31, 42) and 23% (95% CI: 19, 28) and median DOR was 6.7 months (95% CI: 5.6, 9.8) and 5.7 months (95% CI: 4.9, 6.8) in the Datroway and chemotherapy arms, respectively.



The most common adverse reactions (≥20%), including laboratory abnormalities, were stomatitis, nausea, fatigue, decreased leukocytes, decreased calcium, alopecia, decreased lymphocytes, decreased hemoglobin, constipation, decreased neutrophils, dry eye, vomiting, increased ALT, keratitis, increased AST, and increased alkaline phosphatase.

The recommended Datroway dose is 6 mg/kg (maximum of 540 mg for patients ≥90 kg), administered as an intravenous infusion, once every 3 weeks (21-day cycle), until disease progression or unacceptable toxicity.

The approval of Datroway offers a new and promising treatment option for patients with unresectable or metastatic HR-positive, HER2-negative breast cancer who have received prior endocrine-based therapy and chemotherapy. With its improved progression-free survival and objective response rates compared to chemotherapy, Datroway has the potential to significantly impact the lives of patients with this challenging disease. As more data becomes available, healthcare professionals and patients alike can expect to see Datroway become an important addition to the treatment landscape for metastatic breast cancer.