An open-label, single-arm, phase II study of pertuzumab with high-dose trastuzumab for treatment of central nervous system (CNS) progression post-radiotherapy in patients (pts) with HER2-positive metastatic breast cancer (MBC): PATRICIA.

TPS633Background: CNS metastases are observed in up to half of pts with HER2-positive MBC, with incidence likely to rise due to improved systemic treatments and longer overall survival (OS). While radiotherapy can be effective, there are toxicity issues and pts frequently progress. CNS response to existing systemic therapies has been poor; there is no approved treatment for HER2-positive brain metastases in pts with MBC. Combination of the HER2-targeted monoclonal antibodies trastuzumab and pertuzumab provides more comprehensive blockade of HER2 than either agent alone. Trastuzumab concentrations in the CNS increase with an impaired blood–brain barrier (BBB), and preclinical models suggest subtherapeutic levels may be related to insufficient dosing rather than inability to cross the BBB. Higher doses of trastuzumab have not been associated with increased toxicity. PATRICIA is evaluating addition of pertuzumab and high-dose trastuzumab to current systemic treatment for HER2-positive MBC in pts with CNS pro...