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FDA Approval Summary: Datopotamab Deruxtecan-dlnk for Treatment of Patients with Unresectable or Metastatic,
Melanie Royce1, Mirat Shah1, Lijun Zhang1
1Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Abstract:
On January 17, 2025, the FDA approved datopotamab deruxtecan-dlnk (DATROWAY; Dato-DXd), a Trop-2-directed antibody and topoisomerase inhibitor conjugate, for the treatment of adults with unresectable or metastatic, hormone receptor-positive, HER2-negative breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease. Approval was based on results from TROPION-Breast01 (TB01), a multicenter, randomized, open-label trial comparing Dato-DXd with investigator's choice of chemotherapy (ICC). The trial was designed with dual primary endpoints: progression-free survival assessed by blinded independent central review according to RECIST v1.1 and overall survival (OS). TB01 demonstrated a 2-month improvement in median progression-free survival for Dato-DXd compared with ICC (6.9 vs. 4.9 months, respectively; stratified HR, 0.63; 95% confidence interval, 0.52-0.76; P < 0.0001). The OS endpoint was not met; at the final analysis of OS, the median OS was 18.6 months in the Dato-DXd arm and 18.3 months in the ICC arm (HR, 1.01; 95% confidence interval, 0.83-1.22). Although there was no OS improvement, Dato-DXd was also not associated with a clear trend toward potential detriment compared with ICC. The most commonly reported adverse reactions (≥20%) with Dato-DXd were stomatitis, nausea, fatigue, alopecia, constipation, dry eye, keratitis, and vomiting. Overall, the favorable benefit-risk profile for Dato-DXd supported its approval for the intended indication.
Insights
Datopotamab deruxtecan-dlnk (Dato-DXd) is a new FDA-approved breast cancer treatment. It showed improved progression-free survival but not overall survival in patients with HR+/HER2- metastatic breast cancer.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer remains a significant clinical challenge.
- Prior treatment with endocrine-based therapy and chemotherapy is common for patients with advanced disease.
- There is a need for novel therapeutic agents with improved efficacy and manageable safety profiles.
Purpose of the Study:
- To evaluate the efficacy and safety of datopotamab deruxtecan-dlnk (Dato-DXd) compared to investigator's choice of chemotherapy (ICC) in patients with unresectable or metastatic HR+/HER2- breast cancer.
- To assess progression-free survival (PFS) and overall survival (OS) as primary endpoints.
- To determine the benefit-risk profile of Dato-DXd for this patient population.
Main Methods:
- The TROPION-Breast01 (TB01) trial was a multicenter, randomized, open-label study.
- Participants received either Dato-DXd or ICC.
- Key endpoints included PFS assessed by blinded independent central review (BICR) and OS.
Main Results:
- Dato-DXd demonstrated a statistically significant improvement in median PFS compared to ICC (6.9 months vs. 4.9 months; hazard ratio [HR] 0.63).
- The trial did not meet the OS endpoint, with median OS of 18.6 months for Dato-DXd versus 18.3 months for ICC (HR: 1.01).
- Common adverse events with Dato-DXd included stomatitis, nausea, fatigue, and alopecia.
Conclusions:
- Datopotamab deruxtecan-dlnk (Dato-DXd) offers a favorable benefit-risk profile for patients with previously treated unresectable or metastatic HR+/HER2- breast cancer.
- While PFS was improved, the lack of OS benefit warrants further investigation.
- The FDA approval of Dato-DXd provides a new treatment option for this patient group.
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