FDA Approves New ADC for HR+, HER2- Breast Cancer

The US Food and Drug Administration (FDA) has approved datopotamab deruxtecan for the treatment of certain patients with unresectable or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer.

Specifically, the novel Trop-2-directed antibody and topoisomerase inhibitor conjugate is indicated for those who have received prior treatment with endocrine-based therapy and chemotherapy for unresectable or metastatic disease, according to the FDA approval notice.

This approval — the first in the US for the antibody drug conjugate, which was discovered by Daiichi Sankyo and is being jointly developed with AstraZeneca — was based on findings from the randomized, multicenter, open-label TROPION-Breast01trial of 732 patients who were considered unsuitable for further endocrine therapy and who had received up to two lines of prior chemotherapy.

Results showed improved response rates and progression-free survival (PFS) in 365 patients randomized to receive datopotamab deruxtecan (Dato-DXd), compared with 367 randomized to receive investigator’s choice of chemotherapy with eribulin, capecitabine, vinorelbine, or gemcitabine. Median PFS was significantly longer at 6.9 vs 4.9 months in the Dato-DXd and chemotherapy arms, respectively (hazard ratio [HR], 0.63). Median overall survival, at 18.6 and 18.3 months, respectively (HR, 1.01), did not differ significantly in the two arms.

The confirmed overall response rate was 36% and 23%, and the median duration of response was 6.7 and 5.7 months in the Dato-DXd and chemotherapy arms, respectively. 

Adverse reactions occurring in at least 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 alanine aminotransferase, keratitis, increased aspartate aminotransferase, and increased alkaline phosphatase.

Findings from the trial showed that patients who received Dato-DXd had less than half the number of grade 3 or greater toxicities and fewer dose reductions or interruptions than patients who received chemotherapy said first author Aditya Bardia, MD, MPH, at the 2023 European Society of Medical Oncology Congress, as reported by Medscape Medical News. 

The recommended dose of Dato-DXd is 6 mg/kg — with a maximum of 540 mg for patients weighing ≥ 90 kg — given as an intravenous infusion once every 3 weeks until disease progression or unacceptable toxicity, according to the full prescribing information.

Approval in the US follows approval in Japan in December 2024, and the FDA has also 

granted priority review of a Biologics License Application for the use of Dato-DXd for the treatment of certain non-small cell lung cancers, according to Daiichi Sankyo, which noted that “[a] comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, TNBC and HR positive, HER2 low or negative breast cancer.”

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached atsworcester@mdedge.com or on Twitter:@SW_MedReporter.