Dr Tolaney on Evolving First-Line Treatment Approaches in Triple-Negative Breast Cancer

“It is very important for the [triple-negative] subset of breast cancer which has been so challenging for us to treat to see so many highly effective drugs moving in this space.”

Sara Tolaney, MD, MPH, chief of the Division of Breast Oncology and associate director of the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute, and an associate professor of medicine at Harvard Medical School, discussed emerging first-line treatment strategies for patients with advanced triple-negative breast cancer (TNBC), touching on potential shifts in standard of care, novel agents on the horizon, and the importance of making advances in the space.

Tolaney began by remarking that patients with advanced TNBC typically have limited overall survival, and she explained that the introduction of antibody-drug conjugates (ADCs) and other classes of agents to the frontline setting will be important to improve these outcomes. Tolaney specifically mentioned ADCs such as sacituzumab govitecan-hziy (Trodelvy) and datopotamab deruxtecan-dlnk (Dato-DXd; Datroway). Notably, Dato-DXd demonstrated significantly improved efficacy over chemotherapy in PD-L1–negative TNBC in the phase 3 TROPION-Breast02 trial (NCT05374512), and sacituzumab govitecan lowered the risk of disease progression or death vs chemotherapy in the phase 3 ASCENT-03 trial (NCT05382299).

In the phase 3 ASCENT-04/KEYNOTE-D19 study (NCT05382286), sacituzumab govitecan plus pembrolizumab (Keytruda) was evaluated vs chemotherapy plus pembrolizumab in patients with PD-L1–positive, advanced or metastatic TNBC. Findings from the trial showed sacituzumab govitecan plus pembrolizumab significantly improved progression-free survival (PFS) compared with chemotherapy plus pembrolizumab, Tolaney stated.

Tolaney added that she expects sacituzumab govitecan and Dato-DXd to both receive FDA approval and to become new first-line standards of care in metastatic TNBC.

Beyond ADCs, bispecific VEGF x PD-(L)1 antibodies are another class of treatment to watch in the first-line setting for TNBC, Tolaney continued. Tolaney specifically mentioned pumitamig (BNT327) and ivonescimab (SMT112) as bispecific agents that could become first-line options with additional clinical research. The phase 3 ROSETTA Breast-01 trial (NCT07173751) is evaluating first-line pumitamig in combination with physician’s choice of chemotherapy vs placebo plus chemotherapy in patients with TNBC who are ineligible for immunotherapy.

Bispecific antibodies have yielded promising data in the TNBC space, Tolaney added, noting that the field will have to wait and see what results emerge for these agents. Additional research could also show if potential combinations with ADCs are feasible.