Datopotamab Deruxtecan Shows Promising Activity, Safety Among Heavily Pretreated Patients With HR-Positive, HER2-Negative, or Triple-Negative Breast Cancer

According to results from the ongoing phase 1 TROPION-PanTumor01 trial, datopotamab deruxtecan (Dato-DXd), a TROP-2–directed antibody drug conjugate (ADC), demonstrated promising efficacy and safety among heavily pretreated patients with advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, or triple-negative breast cancer. 

“Although recent advances in therapy have improved outcomes, the 5-year survival rate in patients with metastatic disease remains poor,” stated Aditya Bardia, MD, PhD, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, and coauthors. “ADCs aim to address this unmet need by potentially reducing systemic toxicity and improving response rates through selective payload delivery to tumors.” 

This dose-escalation, dose-expansion study enrolled 85 patients with HR-positive, HER2-negative (n = 41), or triple-negative (n = 44) breast cancer who experienced disease progression after local standard treatment. Patients received 6 mg/kg of intravenous datopotamab deruxtecan once every 3 weeks in 21-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent. The primary end points included median objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and safety. 

At the data cut off point, confirmed median ORR was 26.8% in the HR-positive, HER2-negative cohort and 31.8% in the triple-negative cohort. Median DOR was not evaluable in the HR-positive, HER2-negative cohort and 16.8 months in the triple-negative cohort. Median PFS was 8.3 months and 4.4 months, respectively. Due to disease progression, 36 patients discontinued treatment in the HR-positive, HER2-negative cohort and 41 patients discontinued treatment in the triple-negative cohort. Median treatment duration was 4.8 months in the HR-positive, HER2-negative cohort and 4.3 months in the triple-negative cohort. The most common grade ≥3 treatment-related adverse events included stomatitis, nausea, fatigue, vomiting, diarrhea, anemia, and neutropenia. 

As Dr Bardia et al concluded, “In this first-in-human phase I study of Dato-DXd, encouraging antitumor activity and manageable safety profile were observed in patients with heavily pretreated advanced [HR-positive/HER2-negative breast cancer and triple-negative breast cancer].”

“Additional studies are needed to evaluate the mechanisms of resistance to ADCs and to determine the optimal sequence of therapies,” stated Journal of Clinical Oncology senior deputy editor Kathy D. Miller, MD, Indiana University Simon Comprehensive Cancer Center, Indianapolis, Indiana. 

Source: 

Bardia A, Krop IE, Kogawa T, et al. Datopotamab deruxtecan in advanced or metastatic HR+/HER2– and triple-negative breast cancer: Results from the phase I TROPION-PanTumor01 study. J Clin Oncol. Published online: April 23, 2024. doi: 10.1200/JCO.23.01909