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FDA Approves Datopotamab Deruxtecan-dlnk for Advanced HR-Positive, HER2-Negative Breast Cancer


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On January 17, the U.S. Food and Drug Administration (FDA) approved datopotamab deruxtecan-dlnk (Datroway), a TROP-2–directed antibody and topoisomerase inhibitor conjugate, for adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-negative (IHC 0, IHC1+, or IHC2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease.

TROPION-Breast01

Efficacy was evaluated in TROPION-Breast01 (ClinicalTrials.gov identifier NCT05104866), a multicenter, open-label, randomized trial. 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 Eastern Cooperative Oncology Group performance status > 1.

Randomization was stratified by previous lines of chemotherapy, prior CDK4/6 inhibitor treatment, and geographic region. A total of 732 patients were randomly assigned 1:1 to receive either 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, assessed by blinded independent central review based on Response Evaluation Criteria in Solid Tumors version 1.1 and overall survival. Additional efficacy outcomes included confirmed objective response rate and duration of response by blinded independent central review. Median progression-free survival was 6.9 months (95% confidence interval [CI] = 5.7–7.4 months) in the datopotamab deruxtecan-dlnk arm and 4.9 months (95% CI = 4.2–5.5 months) in the chemotherapy arm (hazard ratio [HR] = 0.63, 95% CI = 0.52–0.76, two-sided P < .0001). Median overall survival was 18.6 months (95% CI = 17.3–20.1 months) in the datopotamab deruxtecan-dlnk arm and 18.3 months (95% CI = 17.3–20.5 months) in the chemotherapy arm (HR = 1.01, 95% CI = 0.83–1.22; two-sided P value was not statistically significant). Confirmed objective response rate was 36% (95% CI = 31%–42%) and 23% (95% CI = 19%–28%) and median duration of response was 6.7 months (95% CI = 5.6–9.8 months) and 5.7 months (95% CI = 4.9–6.8 months) in the datopotamab deruxtecan-dlnk and chemotherapy arms, respectively.

The most common adverse reactions (occurring in ≥ 20% of patients), 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 weighing ≥ 90 kg), administered as an intravenous infusion, once every 3 weeks (21-day cycle), until disease progression or unacceptable toxicity.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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