FDA Approves Datopotamab Deruxtecan for HR-Positive/HER2-Negative Metastatic Breast Cancer

Today, the FDA approved datopotamab deruxtecan-dlnk (Datroway, Daiichi Sankyo, Inc.) for adult patients with unresectable or metastatic/HR-positive, HER2-negative breast cancer who have previously received endocrine-based therapy and chemotherapy.1

FDA approves datopotamab deruxtecan-dlnk for HR-positive/HER2-negative metastatic breast cancer. | Image Credit: BHM - stock.adobe.com

The approval is based on findings in TROPION-Breast01 (NCT05104866), a multicenter, open-label, randomized trial, which showed significant improvement in progression-free survival (PFS) with datopotamab deruxtecan-dlnk compared with chemotherapy (6.9 vs 4.9 months; HR, 0.63; P < .0001). While overall survival (OS) was similar between groups, the confirmed objective response rate (ORR) favored datopotamab deruxtecan-dlnk (36% vs 23%).

Datopotamab deruxtecan-dlnk is a Trop-2–directed antibody drug conjugate (ADC), which showed a statistically significant and clinically meaningful improvement in PFS compared with chemotherapy among patients with previously treated HR-positive/HER2-negative inoperable or metastatic breast cancer.2 Findings from the phase 3 TROPION Breast-01 trial were presented during the 2023 San Antonio Breast Cancer Symposium.

The study was designed to evaluate the efficacy and safety of datopotamab deruxtecan-dlnk in patients with unresectable or metastatic HR-positive, HER2-negative breast cancer.1

Eligible patients had experienced disease progression, were unsuitable for further endocrine therapy, and had received 1 to 2 prior lines of chemotherapy for metastatic disease. Key exclusion criteria included a history of or ongoing interstitial lung disease/pneumonitis, clinically active brain metastases, significant corneal disease, or an Eastern Cooperative Oncology Group performance status greater than 1.

A total of 732 patients were randomized 1:1 to receive either datopotamab deruxtecan-dlnk or the investigator’s choice of chemotherapy (eribulin, capecitabine, vinorelbine, or gemcitabine). Randomization was stratified by prior chemotherapy lines, CDK4/6 inhibitor treatment, and geographic region.

The median PFS was 6.9 months (95% CI, 5.7-7.4) in the datopotamab deruxtecan-dlnk arm, compared with 4.9 months (95% CI, 4.2-5.5) in the chemotherapy arm (HR, 0.63; 95% CI, 0.52-0.76; P < .0001). Although median OS was similar between the 2 groups—18.6 months with datopotamab deruxtecan-dlnk vs. 18.3 months with chemotherapy (HR, 1.01; 95% CI, 0.83-1.22)—the confirmed ORR was higher in the datopotamab deruxtecan-dlnk arm at 36% (95% CI, 31-42) compared with 23% (95% CI, 19-28) with chemotherapy. The median duration of response was also longer with datopotamab deruxtecan-dlnk at 6.7 months (95% CI, 5.6- 9.8) vs. 5.7 months (95% CI, 4.9-6.8) in the chemotherapy arm.

Datopotamab deruxtecan-dlnk was associated with several common adverse reactions, occurring in 20% or more of patients. These included stomatitis, nausea, fatigue, and alopecia, along with laboratory abnormalities such as decreased leukocytes, lymphocytes, neutrophils, hemoglobin, and calcium levels. Other frequently reported adverse events were constipation, dry eye, and vomiting. Elevated levels of liver enzymes, including ALT, AST, and alkaline phosphatase, were also observed, as well as keratitis. These findings highlight the need for monitoring and managing potential toxicities associated with the treatment.

The recommended dose of datopotamab deruxtecan-dlnk is 6 mg/kg administered via intravenous infusion every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity occurs.

References

1. FDA approves datopotamab deruxtecan-dlnk for unresectable or metastatic, HR-positive, HER2-negative breast cancer. FDA. January 17, 2025. Accessed January 17, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-datopotamab-deruxtecan-dlnk-unresectable-or-metastatic-hr-positive-her2-negative-breast.

2. Doherty K. Datopotamab deruxtecan prolongs PFS in HR+/HER2- inoperable or metastatic breast cancer. OncLive. December 7, 2023. Accessed January 17, 2025. https://www.onclive.com/view/datopotamab-deruxtecan-prolongs-pfs-in-hr-her2--inoperable-or-metastatic-breast-cancer.