QSPC-12 CNS-Only Disease Is Associated With Longer Survival but High CNS-Related Mortality in Patients With Her2+ Breast Cancer

BACKGROUND Due to poorer drugs efficacy in the CNS than extracranially, patients with metastatic HER2+ breast cancer and CNS-only disease are a growing population. Here, we aimed to report the overall survival (OS) and CNS-related death in HER2+ MBC patients with CNS metastasis by disease distribution. METHODS Patients with HER2+ MBC with CNS disease including BrM, leptomeningeal (LMD) and/or dural metastasis treated in our Institution between 8/2010 and 4/2022 were included. Extracranial metastasis (ECM) was evaluated at the time of CNS metastasis and at last follow-up/death. CNS-related death was defined as death from tumor-related brain injury, functional deficits/seizures, and/or complications of brain-directed therapies. OS was estimated using Kaplan-Meier methodology. RESULTS The cohort comprised 274 patients. At CNS metastasis diagnosis, 72/274 (26%) presented with CNS-only disease (63 without prior ECM diagnosis, and 9 with prior ECM in complete response), and 200/274 (73%) with concomitant ECM. Two patients had unknown ECM status at CNS disease diagnosis. Among patients with CNS-only disease, 34/72 (47%) never developed ECM progression by the time of their last follow-up/death. Patients with CNS-only disease had longer OS than patients with CNS+ECM: 3.48 years (95%CI: 2.10-5.14) versus 1.96 years (95%CI: 1.62-2.27), respectively (p=0.017).The cumulative incidence of CNS-related death at 3 years was 32.91% (27.2-38.7%), and did not differ between CNS+ECM versus CNS-only groups, p=0.14, despite higher use of neurosurgical resection in the latter group. Conversely, death due to other causes was more likely to occur in the CNS+ECM group than CNS-only, p=<0.001. LMD and whole-brain radiotherapy were independently associated with CNS-related death [HR=1.88 (95%CI: 1.20-2.95), p=0.006; HR=1.69 (95%CI: 1.12-2.54), p=0.01]. CONCLUSIONS With higher rates of local therapy, patients with CNS-only disease had longer survival but high rates of CNS-related death owing to the treatable but ultimately refractory disease nature. Novel therapies with CNS efficacy are urgently needed.