Datopotamab deruxtecan-dlnk is approved by the USFDA for unresectable or metastatic, HR-positive, HER2-negative breast cancer

On January 17, 2025, the Food and Drug Administration sanctioned datopotamab deruxtecan-dlnk (Datroway, Daiichi Sankyo, Inc.), a Trop-2-targeted antibody and topoisomerase inhibitor conjugate, for adult patients with unresectable or metastatic, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+, or IHC 2+/ISH-) breast cancer who have previously undergone endocrine-based therapy and chemotherapy for unresectable or metastatic disease. Effectiveness and Safety The efficacy was assessed in TROPION-Breast01 (NCT05104866), a multicenter, open-label, randomized study. Patients must have undergone disease progression, been considered inappropriate for additional endocrine therapy, and received one or two prior lines of chemotherapy for unresectable or metastatic illness. Patients were eliminated due to a history of interstitial lung disease/pneumonitis necessitating steroids, active interstitial lung disease/pneumonitis, clinically active brain metastases, or substantial corneal disease. Patients were also excluded for an ECOG performance status greater than 1. Randomization was stratified according to past lines of chemotherapy, previous treatment with CDK4/6 inhibitors, and geographical area. A total of 732 patients were randomized in a 1:1 ratio to receive either datopotamab deruxtecan-dlnk (n=365) or the investigator’s choice of chemotherapy (n=367), which included eribulin (60%), capecitabine (21%), vinorelbine (10%), or gemcitabine (9%). The primary efficacy outcome measures were progression-free survival (PFS), evaluated by blinded independent central review (BICR) according to RECIST v1.1, and overall survival (OS). Supplementary efficacy outcomes encompassed the confirmed objective response rate (ORR) and the duration of response (DOR) as assessed by BICR. The median progression-free survival (PFS) was 6.9 months (95% CI: 5.7, 7.4) for the datopotamab deruxtecan-dlnk group and 4.9 months (95% CI: 4.2, 5.5) for the chemotherapy group, with a hazard ratio of 0.63 (95% CI: 0.52, 0.76) and a two-sided p-value of less than 0.0001. The median overall survival (OS) was 18.6 months (95% CI: 17.3, 20.1) for the datopotamab deruxtecan-dlnk group and 18.3 months (95% CI: 17.3, 20.5) for the chemotherapy group, with a hazard ratio of 1.01 (95% CI: 0.83, 1.22); the two-sided p-value was not statistically significant. The confirmed overall response rate (ORR) was 36% (95% CI: 31, 42) and 23% (95% CI: 19, 28), while the median duration of response (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 groups, respectively. The predominant adverse reactions (≥20%), encompassing laboratory abnormalities, included stomatitis, nausea, fatigue, leukopenia, hypocalcemia, alopecia, lymphopenia, anemia, constipation, neutropenia, dry eye, vomiting, elevated ALT, keratitis, elevated AST, and increased alkaline phosphatase levels. The advised dosage of datopotamab deruxtecan-dlnk is 6 mg/kg (with a maximum of 540 mg for patients weighing ≥90 kg), delivered via intravenous infusion once every three weeks (21-day cycle), unless disease progression or intolerable toxicity occurs.