Brain metastasis as first and only metastatic relapse site portends poor outcomes in patients with advanced HER2+ breast cancer.

Abstract

1045 Background: In patients (pts) with stable or no extracranial disease (ECD) presenting with breast cancer brain metastases (BCBrMs), current guidelines recommend pts receive local therapy with radiation +/- surgery, without changing systemic therapy. However, preliminary studies suggest that pts with isolated HER2+ BCBrM without ECD have inferior overall survival (OS) compared to pts with concurrent ECD. Our study further explores the implications of ECD status on intracranial progression free survival (iPFS) and OS. Methods: Retrospective analysis was performed on data from 153 pts diagnosed with initial HER2+ BCBrM who received CNS radiation at Duke between 2008 and 2020. Demographics, dates of metastatic and BCBrM diagnosis, ECD status at first CNS event, systemic therapy, and outcomes were collected. The primary endpoint was iPFS defined as the time from first CNS radiation to the subsequent documentation of intracranial progression (RANO-BM). OS was defined as time from first CNS radiation and first metastatic disease to date of death or last known contact. ECD status was defined by RECIST1.1 from systemic staging scans within 30 days of first CNS event. Results: In this cohort of 153 pts with HER2+ BCBrMs undergoing CNS radiation, > 70% of pts with known ECD status had controlled systemic disease: either no ECD (27%) or stable/responding disease (44%). 64% of pts’ tumors were ER+. Median age was 50 years (range 24 – 75). Most pts (59%) developed first CNS event during adjuvant or 1st/2nd line metastatic therapy. CNS radiation treatment included 48% of pts receiving SRS only, 9% WBRT only, and 43% SRS and WBRT. All pts with no ECD presented with isolated BCBrMs as first metastatic disease. Among pts with known ECD status, OS from initial metastatic disease to death was markedly worse for pts with isolated brain metastases or no ECD (median = 28.4m, 95% CI: 18.1 to not reached) compared to those with progressive or stable/responding ECD (48.8m, 95% CI: 40.5 to 65.0; and 68.1m, 95% CI: 55.2 to 85.7, respectively; log-rank p = 0.004). OS from first CNS involvement to death was significantly worse for pts with progressive ECD (17.8m, 95% CI: 13.7 to 28.8) versus stable/responding (36.6m, 95% CI: 29.7 to 45.2) or no ECD (28.4m, 95% CI: 18.1 to not reached; log-rank p = 0.008). iPFS did not differ statistically among subgroups of pts with known ECD status: progressive ECD (median = 7.7m), no ECD (8.3m), or stable/responding ECD (11.2m) (log-rank p = 0.15). Conclusions: Overall survival in pts with HER2+ isolated BCBrM was markedly inferior to that of pts with progressive or stable/responding ECD. Studies investigating initiation of brain penetrable HER2-targeted therapies earlier in the disease course of isolated HER2+ BCBrMs pts are warranted.