Dr Graff on the Investigation of Datopotamab Deruxtecan in HR+ Breast Cancer and TNBC

Stephanie L. Graff, MD, director, breast oncology, Lifespan Cancer Institute, assistant professor of medicine, Warren Alpert Medical School, co-leader, Breast Cancer Translational Research Disease Group, Brown University’s Legorreta Cancer Center, discusses current and planned investigations of the emerging antibody-drug conjugate (ADC) datopotamab deruxtecan (Dato-DXd) in patients with metastatic hormone receptor (HR)–positive breast cancer and triple-negative breast cancer (TNBC).

There is substantial interest in developing the emerging Trop-2–targeting ADC Dato-DXd within the breast cancer space. Previous data on this agent’s use in patients with advanced solid tumors were reported from the phase 1 TROPION-PanTumor01 trial (NCT03401385), Graff begins. The multicenter dose-escalation/expansion trial included those with non–small cell lung cancer, as well as those with metastatic TNBC and HR-positive, HER2-negative breast cancer.

Data from an updated analysis of the TNBC cohort (n = 44) presented at the 2022 San Antonio Breast Cancer Symposium showed that Dato-DXd elicited objective responses in patients with heavily pretreated metastatic TNBC regardless of whether they had previously undergone treatment with topoisomerase I inhibitor–based ADCs, Graff reports. In patients who had progressed on standard treatment, Dato-DXd elicited an objective response rate (ORR) of 32%; this was comprised of 1 complete response (CR) and 13 partial responses (PR). The subgroup of patients who had been treated with topoisomerase I inhibitor–based ADCs (n = 27) experienced an ORR of 44%, which included 1 CR and 11 PRs. Results from the HR-positive, HER2-negative cohort of the trial also experienced encouraging and durable responses with Dato-DXd, according to Graff.

Results from TROPION-PanTumor01 have supported the launch of several ongoing trials that will continue investigating Dato-DXd in these spaces, Graff adds. For example, the phase 3 TROPION-Breast02 trial (NCT05374512) will further evaluate the efficacy and safety of Dato-DXd in patients with TNBC. Additionally, the phase 3 TROPION-Breast01 study (NCT05104866) will compare Dato-DXd with physician’s choice of treatment in patients with metastatic HR-positive breast cancer who have progressed on prior endocrine therapy and 1 or 2 prior lines of chemotherapy.

Disclosures: Dr Graff reports serving in a consultory or advisory role for AstraZeneca, Daiichi Sankyo, Eli Lilly, Genentech, Novartis, Pfizer, Seattle Genetics.