Dr Lin on the Safety of T-DXd for HER2+ Breast Cancer With/Without 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, medicine, Harvard Medical School, discusses how the safety data from the phase 3 DESTINY-Breast12 trial (NCT04739761) compare with the known safety profile of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) in patients with HER2-positive advanced or metastatic breast cancer with or without brain metastases.

In DESTINY-Breast12, the safety data for T-DXd largely aligned with previously reported adverse effects (AEs) in other T-DXd trials, particularly regarding common adverse effects (AEs), such as nausea and fatigue, Lin begins. Although the cohorts with and without brain metastases were not statistically compared, the AE profiles appeared similar across both groups, and there were no unique safety concerns specific to the brain metastases population, she explains.

AEs of particular interest included interstitial lung disease (ILD) and cardiac dysfunction, Lin continues. Cardiac dysfunction was observed infrequently, with no cases of severe (grade 4 or 5) left ventricular ejection fraction (LVEF) reduction. Only 2 cases of moderate (grade 3) LVEF decrease were reported in patients with brain metastases, both of which were reversible upon intervention, she reports.

However, ILD presented a more notable safety signal, according to Lin. Six cases of grade 5 ILD occurred in the brain metastases cohort, and 3 grade 5 cases appeared in the cohort without brain metastases, she expands. Importantly, among the 6 patients with brain metastases with ILD, 4 had concurrent infections, including 3 instances of pneumocystis pneumonia (PCP) and 1 instance of aspergillosis, Lin notes. This raised questions about the connection between T-DXd, ILD, and these opportunistic infections, Lin explains. It remains unclear whether T-DXd independently contributed to ILD in these cases or whether the ILD was primarily related to the coexisting infections, she says. These findings underscore the importance of PCP prophylaxis in patients treated with T-DXd, she concludes.