Dr Lin on the Importance of the DESTINY-Breast12 Trial for T-DXd Use in HER2+ Breast Cancer With Brain Metastases

Nancy U. Lin, MD, associate chief, Division of Breast Oncology, Dana-Farber Cancer Institute, Susan F. Smith Center for Women’s Cancers, director, Metastatic Breast Cancer Program, Program for Patients with Breast Cancer Brain Metastases, senior physician, associate professor of medicine, Harvard Medical School, discusses the rationale and clinical importance of data from the phase 3 DESTINY-Breast12 trial (NCT04739761) in patients with HER2-positive advanced or metastatic breast cancer with or without brain metastases. Notably, this investigation evaluated treatment with fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu).

Prior to the DESTINY-Breast12 study, the body of evidence for T-DXd in patients with HER2-positive brain metastases comprised data from small prospective trials and retrospective analyses of larger phase 3 studies, Lin begins. These trials demonstrated intracranial response rates ranging from 44% to 73% with the agent for patients with HER2-positive breast cancer and brain metastases, she states. However, most of these studies either included only patients with stable brain metastases or were limited by their retrospective nature, Lin notes. Accordingly, there was a need for prospective data from patients with active brain metastases to better reflect real-world scenarios, she says.

DESTINY-Breast12 aimed to address this gap by evaluating the efficacy of T-DXd in a large, international, prospective phase 3b/4 trial that included patients both with and without brain metastases, Lin explains. Data from the study, presented during the 2024 ESMO Congress, demonstrated significant intracranial activity with T-DXd in patients with HER2-positive metastatic breast cancer, including those with stable and active brain metastases.

Among the cohort of patients with baseline brain metastases (n = 263), the primary end point was progression-free survival (PFS). The 12-month PFS rate was 61.6% (95% CI, 54.9%-67.6%), with a median PFS of 17.3 months (95% CI, 13.7-22.1). The PFS rates were consistent across patients with stable (62.9%) and active brain metastases (59.6%), highlighting the durability of the treatment. In patients with active brain metastases, those with previously untreated disease had a slightly lower 12-month PFS rate (47.0%); those with previously treated disease showed a 12-month PFS rate of 66.7%.

These findings affirm T-DXd's role as a standard of care in the second-line setting for patients without brain metastases, Lin emphasizes. More importantly, this provides a potential therapeutic option for patients with brain metastases, including those with active and previously untreated disease, she concludes.

Disclosures: Dr Lin reports consultant/advisory/steering committee participation with Artera, AstraZeneca, Bluepoint Medicines, Daiichi Sankyo, Eisai, Janssen, Olema Pharmaceuticals, Seagen, and Stemline Therapeutics; travel support from Olema Pharmaceuticals; institutional research support from AstraZeneca, Genentech, Olema Pharmaceuticals, Pfizer, Seagen, and Zion Pharmaceuticals; and royalties from book chapters from UpToDate.