CMET-25. PROGRESSION-FREE SURVIVAL (PFS) AND SITE OF FIRST PROGRESSION IN HER2+ METASTATIC BREAST CANCER PATIENTS WITH OR WITHOUT BRAIN METASTASES: A POOLED ANALYSIS OF TUCATINIB PHASE I STUDIES

Abstract

Background: Brain metastases (BM) are frequent in HER2+ MBC occurring in>30% of pts and are associated w significant neurologic morbidity and mortality. Current treatment strategies for BM primarily utilize radiotherapy (RT) and in selected instances surgical resection. Tucatinib is a highly selective oral HER2+ tyrosine kinase inhibitor that has shown promising results in HER2+ MBC both in pts w and w/o BM. Methods: Two Phase 1b studies of tucatinib were pooled to compare PFS and sites of relapse in pts w or w/o BM. Results: 77 pts were analyzed, all treated at the recommended Phase 2 dose of 300mg PO BID of tucatinib, 50 in the 004 trial (tucatinib + T-DM1) and 27 in the 005 trial (tucatinib + trastuzumab +capecitabine). All pts were heavily pretreated w a median of 3 prior therapies including a taxane, trastuzumab, pertuzumab, T-DM1 and lapatinib. Four cohorts of pts were identified: 46% (35) had systemic metastases only, 17% (13) had previously treated (RT w or w/o surgery) and stable BM, 19% (15) had previously treated and progressive BM and 17% (13) had asymptomatic untreated BM demonstrated by screening MRI. Median PFS across cohorts was 8.5, 6.1, 9.0 and 7.1 months, respectively. No statistically significant difference in PFS was seen when comparing the non-BM cohort to all BM cohorts (median of 8.5 vs. 6.7 months; p=0.65). The risk of progression in brain in pts w baseline BM was 48.8% overall (41.5% in brain only; 7.3% in brain and body) compared to an 11.1% overall (8.3% in brain only; 2.8% in brain and body) in pts w/o baseline BM. Conclusions: 54% of pts entered tucatinib studies w baseline BM, either previously treated (stable or progressive) or untreated. The cohorts of pts analyzed appear to differ only in the site of disease progression. Although pts w/o baseline BM primarily have progression in extraneural sites and pts w baseline BM primarily have progression in the CNS, PFS is comparable across cohorts. Furthermore, pts both w and w/o BM have durable responses w these combination therapies following multiple lines of prior HER2 targeted therapy. These data support the use of tucatinib in both pts w and w/o BM in the accruing HER2CLIMB trial.