TBCRC 018: Phase II study of iniparib in combination with irinotecan to treat progressive triple negative breast cancer brain metastases. Homo sapiens

Approximately half of women diagnosed with advanced triple negative breast cancer (TNBC) will develop brain metastases, of which the majority will have uncontrolled extracranial disease. While local therapies to treat brain metastases are standardly prescribed, survival remains less than 6 months. This phase II, multi-center trial evaluated efficacy of irinotecan and iniparib, anti-cancer agents with activity in TNBC and known to cross the blood brain barrier, among 34 patients with new or progressive TNBC brain metastases. While time to progression was short (2.1 months), 27% of patients experienced intracranial clinical benefit and therapy was well-tolerated. Correlative studies illustrate partial response was associated with germline BRCA mutation status and high tumor expression of proliferation genes and signatures. To our knowledge, this is the first study showing feasibility of enrolling patients with progressive TNBC brain metastases to a systemic therapy and lays the groundwork for future studies to treat this devastating disease. Overall design: 24 tumor FFPE samples of this trial, representing 21 individual patients, were gene expression profiled. Expression of 128 selected genes was evaluated, including 5 HK genes.