Datroway Approved in the U.S. for Previously Treated Metastatic HR Positive, HER2 Negative Breast Cancer

Datroway, a Trop-2-directed antibody and topoisomerase inhibitor conjugate, has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of 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 is based on the results of the TROPION-Breast01 trial, which demonstrated the drug's efficacy and safety in this patient population.

The TROPION-Breast01 trial was a multicenter, open-label, randomized trial that enrolled 732 patients who had experienced disease progression, were deemed unsuitable for further endocrine therapy, and had received one or two lines of prior chemotherapy for unresectable or metastatic disease. Patients were excluded for a history of ILD/pneumonitis requiring steroids, ongoing ILD/pneumonitis, clinically active brain metastases, or clinically significant corneal disease. Patients also were excluded for ECOG performance status >1.

Randomization was stratified by previous lines of chemotherapy, prior CDK4/6 inhibitor treatment, and geographical region. A total of 732 patients were randomized (1:1) to datopotamab deruxtecan-dlnk (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 datopotamab deruxtecan-dlnk 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 datopotamab deruxtecan-dlnk 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 datopotamab deruxtecan-dlnk 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 datopotamab deruxtecan-dlnk 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.



In conclusion, the approval of Datroway in the U.S. for previously treated metastatic HR-positive, HER2-negative breast cancer represents a significant milestone in the treatment of this patient population. The drug's demonstrated efficacy and safety profile, as well as its potential to improve progression-free survival and overall response rates compared to chemotherapy, make it an attractive option for patients and healthcare providers. As regulatory submissions for Datroway in breast cancer are under review in the EU, China, and other regions, the drug's potential market size and growth prospects are promising. Investors and healthcare professionals should closely monitor the drug's progress and consider its potential impact on the breast cancer treatment landscape.