FDA Approves Dato-DXd in HR+/HER2– Breast Cancer

• The FDA has approved datopotamab deruxtecan (Dato-DXd) for the treatment of patients with unresectable or metastatic hormone receptor-positive (HR+), HER2-negative (HER2–) breast cancer who have received prior systemic therapy.
• Dato-DXd is a TROP2-directed antibody-drug conjugate that has shown to be more active in this patient population than chemotherapy.
• Findings from the phase 3 TROPION-Breast01 trial (NCT05104866) support this regulatory decision.

The FDA has approved Dato-DXd, a TROP2-directed ADC, for the treatment of patients with HR+, HER2– breast cancer that has been previously treated with systemic therapy.¹

This approval is supported by findings from the phase 3 TROPION-Breast01 trial (NCT05104866). The median progression-free survival (PFS) was 6.9 months (95% CI, 5.7-7.4) in the Dato-DXd arm and 4.9 months (95% CI, 4.2-5.5) in the chemotherapy arm (HR, 0.63; 95% CI, 0.52-0.76; two-sided P-value <.0001).

The median overall survival (OS) was 18.6 months (95% CI, 17.3-20.1) in the Dato-DXd 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). The confirmed overall response rate (ORR) was 36% (95% CI, 31-42) and 23% (95% CI, 19-28) and 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 Dato-DXd and chemotherapy arms, respectively.

According to progression-free survival (PFS) findings presented at the 2023 San Antonio Breast Cancer Symposium,³ at 6 months, the PFS rates were 53.3% vs 38.5%, respectively, and at 12 months, these rates were 25.5% vs 14.6%.

“Dato-DXd is a TROP2-directed antibody-drug conjugate. This was studied in the phase 3 TROPION-Breast01trial, which was a global study that enrolled patients with hormone receptor-positive, HER2– advanced disease who had received 1 to 2 prior lines of chemotherapy,” said Tanya Gupta, MD, medical oncologist in the Stanford University Department of Medicine, Division of Medical Oncology, in an interview with Targeted Oncology^TM.

In TROPION-Breast01, Dato-DXd was compared with the investigator's choice of chemotherapy in patients with inoperable or metastatic HR+, HER2– breast cancer who have received 1 or 2 prior lines of systemic therapy. The estimated enrollment was 732 patients across sites in 10 states in the US and 19 additional countries.⁴

PFS and overall survival served as the primary end points of the study. Secondary end points included ORR, duration of response, PFS by investigator assessment, disease control rate, time to first subsequent therapy, and time to second subsequent therapy.

For safety, the most common adverse events (≥20%), including laboratory abnormalities, consisted of stomatitis, nausea, fatigue, decreased leukocytes, decreased calcium, alopecia, decreased lymphocytes, decreased hemoglobin, constipation, decreased neutrophils, dry eye, vomiting, increased alanine aminotransferase, keratitis, increased aspartate aminotransferase, and increased alkaline phosphatase.

According to the FDA, the recommended dose of Dato-DXd is 6 mg/kg (maximum of 540 mg for patients ≥90 kg), administered via intravenous infusion, once every 3 weeks on a 21-day cycle, until disease progression or unacceptable toxicity.

REFERENCES:

1. FDA approves datopotamab deruxtecan-dlnk for unresectable or metastatic, HR-positive, HER2-negative breast cancer. News release. FDA. January 17, 2025. Accessed January 17, 2025. https://tinyurl.com/2nf2nnyk

2. Datopotamab deruxtecan significantly extended progression-free survival vs. chemotherapy in patients with HR-positive, HER2-low or negative breast cancer in TROPION-Breast01 phase III trial. News release. AstraZeneca. October 23, 2023. Accessed October 28, 2024. https://tinyurl.com/yc2m973a

3. Bardia A, Jhaveri K, Im SA, et al. Randomized phase 3 study of datopotamab deruxtecan vs chemotherapy for patients with previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative breast cancer: results from TROPION-Breast01. Presented at: 2023 San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, TX. Abstract GS02-01

4. A phase-3, open-label, randomized study of Dato-DXd versus investigator's choice of chemotherapy (ICC) in participants with inoperable or metastatic HR-positive, HER2-negative breast cancer who have been treated with one or two prior lines of systemic chemotherapy (TROPION-Breast01). ClinicalTrials.gov. Updated August 20, 2024. Accessed October 28, 2024. https://clinicaltrials.gov/study/NCT05104866