On 17 January 2025, the US 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-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.
Efficacy was evaluated in TROPION-Breast01 (NCT05104866), a multicentre, open-label, randomised study. Patients must have experienced disease progression, been deemed unsuitable for further endocrine therapy, and have received one or two lines of prior chemotherapy for unresectable or metastatic disease. Patients were excluded for a history of interstitial lung disease (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.
Randomisation was stratified by previous lines of chemotherapy, prior CDK4/6 inhibitor treatment, and geographical region. A total of 732 patients were randomised 1:1, 365 to datopotamab deruxtecan-dlnk and 367 to investigator’s choice of chemotherapy: 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% confidence interval [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 [HR] 0.63, 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 (HR 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 haemoglobin, 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.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
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