NVTG-11 EFFICACY OF TRASTUZUMAB DERUXTECAN IN HER2-POSITIVE AND HER2-LOW BREAST CANCER WITH ACTIVE BRAIN METASTASES

Trastuzumab deruxtecan (T-DXd) has demonstrated strong CNS penetrance for HER2+ breast cancer with brain involvement, but further evidence is needed to support the use of T-DXd in HER2-low patients. This institutional retrospective review investigates the efficacy of T-DXd between HER2+ and HER2-low breast cancers with active brain metastases (BM). Using the Stanford Research Repository from 2020-2023, we identified 36 patients with breast cancer and active BM treated with T-DXd. Out of the 36, 7 had HER2+ breast cancer and 29 had HER2-low breast cancer. Of the 7 HER2+ patients, 6 are still living with 5 still continuing on treatment while median survival of the 29 HER2-low patients was 18 months (95%LCL 7 with indeterminate UCL based on available data) with 12 still living and 2 continuing on treatment. Using RANO-BM criteria we measured intracranial objective response rate (ORR-IC) on MRI for those with available target lesion measurements at initiation and end of treatment (EOT) windows (n=33). Of the HER2+ patients (n=7), 1/7 (14%) showed complete response, 2/7 (29%) had partial response, 3/7 (43%) had stable disease, and 1/7 (14%) had progressive disease with a notable 73.7% reduction in size of target lesions but numerous new enhancing lesions at EOT. In contrast, of the HER2-low cohort (n=26), 6/26 (23%) demonstrated partial response, 8/26 (31%) had stable disease, and 12/26 (46%) had progressive disease. Of the 12 HER2-low patients with progressive disease, 2/12 had >30% reduction in size of target lesions but numerous new lesions at EOT. Despite some intracranial responses in HER2-low patients, their median survival and high progression rates indicate limited benefits, highlighting the need for more robust prospective studies to further investigate T-DXd’s efficacy in this subgroup.