FDA approves datopotamab deruxtecan-dlnk for unresectable or metastatic, HR-positive, HER2-negative breast cancer
Regulatory approval: On Jan 17, 2025, the FDA approved datopotamab deruxtecan-dlnk (Datroway), a Trop-2–directed antibody–topoisomerase inhibitor conjugate, for adults with unresectable or metastatic HR-positive, HER2-negative breast cancer (IHC 0/1+ or IHC2+/ISH−) previously treated with endocrine-based therapy and chemotherapy for unresectable/metastatic disease. Approval was supported by TROPION-Breast01, which showed improved PFS vs investigator’s choice chemotherapy, while OS was not statistically significant.
FDA approval (Jan 17, 2025)
The 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, HR-positive, HER2-negative breast cancer (IHC 0, IHC1+, or IHC2+/ISH−) who have received prior endocrine-based therapy and chemotherapy for unresectable/metastatic disease.
Supporting trial: TROPION-Breast01 (NCT05104866)
Multicenter, open-label, randomized trial in patients with progression, deemed unsuitable for further endocrine therapy, and who had 1–2 prior chemotherapy lines for unresectable/metastatic disease. Key exclusions included history of ILD/pneumonitis requiring steroids, ongoing ILD/pneumonitis, clinically active brain metastases, clinically significant corneal disease, and ECOG >1.
Randomization (1:1; n=732): datopotamab deruxtecan-dlnk (n=365) vs investigator’s choice chemotherapy (n=367): eribulin (60%), capecitabine (21%), vinorelbine (10%), gemcitabine (9%).
Efficacy (BICR, RECIST v1.1):
- Median PFS: 6.9 vs 4.9 months; HR 0.63 (95% CI 0.52–0.76), p<0.0001
- Median OS: 18.6 vs 18.3 months; HR 1.01 (95% CI 0.83–1.22), not statistically significant
- ORR: 36% vs 23%; median DOR: 6.7 vs 5.7 months
Safety and dosing (label highlights)
Common adverse reactions (≥20%, incl labs) included stomatitis, nausea, fatigue, cytopenias, alopecia, constipation, dry eye, vomiting, elevated ALT/AST/alkaline phosphatase, keratitis.
Recommended dose: 6 mg/kg IV (max 540 mg if ≥90 kg) every 3 weeks until progression or unacceptable toxicity.