Phase 2 study of tucatinib-trastuzumab-capecitabine for leptomeningeal metastasis in women with HER2-positive breast cancer

As new therapie extend the survival of cancer patients, leptomeningeal metastasis (LM) has become increasingly prevalent as a late-stage complication of systemic solid cancers. The phase 2 TBCRC049 trial at MD Anderson Cancer Center (Houston, TX) evaluated the combination of tucatinib with trastuzumab and capecitabine for newly diagnosed LM from HER2-positive breast cancer (HER2+ BC). Among 17 enrolled women, 15 (88%) were symptomatic and 8 (47%) had abnormal cerebrospinal fluid cytology. The trial met it prespecified interim efficacy threshold and exceeded the historical control of 4.4 months. The median overall survival was 10 months (95% CI 4.1-NR), wherease the median time to CNS progression was 6.9 months (2.8-13.8), and the median progression-free survival was 4.1 months (2,3-11.4). Of 13 response-evaluable patients, 5 (38%) achieved composite LM objective response, and of 12 evaluable patients, 7 (58%) had improved neurological deficits. The authors conclude that these data support systemic therapy as an approach in HER2+ BC LM.