The Food and Drug Administration (FDA) approved the DATROWAY® (datopotamab deruxtecan-dlnk) intravenous injection on January 17, 2025. It is manufactured by Daiichi Sankyo pharmaceutical company, in Japan. DATROWAY® is an antibody-drug conjugate mainly targeting tumor-associated calcium signal transducer 2 (Trop-2) which includes topoisomerase inhibitors. It is indicated for the treatment of 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 received endocrine-based therapy and chemotherapy for unresectable or metastatic disease.
The safety and efficacy of DATROWAY were assessed using the clinical study TROPION-Breast01 (NCT05104866). A total of 732 patients (median age = 55 years, 99% female, 48% white, 41% Asian, 1.5% black or African American, 11% Hispanic/Latino ethnicity) with unresectable or metastatic HR-positive, HER2-negative breast cancer were included in this multicenter, open-label and randomized clinical trial. Exclusion criteria included patients with corneal disease, a history of active interstitial lung disease (ILD), brain metastases, or an Eastern Cooperative Oncology Group (ECOG) performance status (PS) > 1.
Out of the included patients, 57% had an ECOG PS of 0 while 42% had an ECOG PS of 1. All patients were randomized (1:1) to DATROWAY or the investigator’s choice of chemotherapy including 60% eribulin, 21% capecitabine, 10% vinorelbine, or 9% gemcitabine. The efficacy outcomes such as progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) were evaluated by blinded independent central review (BICR). The PFS was measured based on response evaluation criteria in solid tumors (RECIST) v.1.1 and overall survival (OS).
The median PFS was 6.9 months (95% confidence interval [CI]: 5.7, 7.4) and 4.9 months (95% CI: 4.2, 5.5) in the DATROWAY group and chemotherapy group, respectively, with a hazard ratio (HR) of 0.63 (95% CI: 0.52, 0.76) and a two-sided p-value < 0.000. However, no statistically significant difference was observed in OS between the two groups. The median OS was found to be 18.6 months (95% CI: 17.3, 20.1) and 18.3 months (95% CI: 17.3, 20.5) in the DATROWAY group and chemotherapy group, respectively (HR 1.01 [95% CI: 0.83, 1.22]). The confirmed ORR was 36% (95% CI: 31, 42) in the DATROWAY group and 23% (95% CI: 19, 28) in the chemotherapy group. Moreover, the median DOR was found to be 6.7 months (95% CI: 5.6, 9.8) and 5.7 months (95% CI: 4.9, 6.8) in the DATROWAY group and chemotherapy groups, respectively.
Serious adverse events were reported in 15% of patients in the DATROWAY group including urinary tract infection (1.9%), coronavirus disease (COVID-19) (1.7%), ILD/pneumonitis (1.1%), nausea, vomiting, diarrhea, anemia, pulmonary embolism, and acute kidney injury (0.6% each). Additionally, 0.3% of patients receiving DATROWAY were reported with Fatal adverse reactions due to ILD/pneumonitis.
Approximately 20% of patients were reported with the most common adverse events such as nausea, stomatitis, vomiting, alopecia, dry eye, keratitis, constipation, decreased levels of leukocytes, lymphocytes, calcium, hemoglobin, neutrophils, ALT along with increased levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase.
The recommended dosage of DATROWAY® is 6 mg/kg, administered as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or intolerable toxicity occurs. If the scheduled dose is missed or delayed, administer it as soon as possible and do not wait for the next planned cycle. Adjust the administration schedule to ensure a 3-week interval is maintained between doses.
Reference: Food and Drug Administration. FDA approves datopotamab deruxtecan-dlnk for unresectable or metastatic, HR-positive, HER2-negative breast cancer. Published 17 January 2025. Accessed 20 January 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-datopotamab-deruxtecan-dlnk-unresectable-or-metastatic-hr-positive-her2-negative-breast
