Dr Tolaney on the Potential Role for Sac-TMT With/Without Pembrolizumab in HR+, HER2– Breast Cancer

“I’m excited about potentially having an immunotherapy option for patients with metastatic, HR-positive disease. I do believe there may be merit to combining an ADC with a checkpoint inhibitor.”

Sara M. Tolaney, MD, MPH, chief of the Division of Breast Oncology, associate director of the Susan F. Smith Center for Women's Cancers, and a senior physician at Dana-Farber Cancer Institute; as well as an associate professor of medicine at Harvard Medical School, discusses the potential clinical utility of the antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT) as monotherapy or in combination with pembrolizumab (Keytruda) for the treatment of patients with hormone receptor (HR)–positive, HER2-negative unresectable or locally advanced metastatic breast cancer.

Sac-TMT is currently being evaluated for the treatment of patients with HR-positive, HER2-negative breast cancer who have not been previously treated with chemotherapy in the metastatic setting in the phase 3 TroFuse-010 study (NCT06312176). The open-label study is randomly assigning approximately 1200 patients 3:3:2 to receive sac-TMT monotherapy, sac-TMT plus pembrolizumab, or physician’s choice of chemotherapy, which comprises paclitaxel plus nab-paclitaxel, capecitabine, or liposomal doxorubicin. The primary end point of the study is progression-free survival per RECIST 1.1 criteria as assessed by blinded independent central review; secondary end points include overall survival, objective response rate, duration of response, and safety and tolerability.

Tolaney noted that if the TroFuse-010 trial is successful, it could bring a new ADC into the frontline setting for patients with HR-positive, HER2-negative unresectable or locally advanced metastatic breast cancer. Currently, the only FDA-approved ADC in the first line setting is fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu). However, this agent is only indicated for patients with some level of HER2 expression, she added.

It is exciting to have a potential immunotherapy option on the horizon for the treatment of patients with HR-positive, HER2-negative disease, Tolaney stated. There also may be merit for combining an ADC with a checkpoint inhibitor in the frontline setting, which could produce even better outcomes for patients, she concluded.