There is an unmet need for evidence-based systemic therapies for patients with HER2+ metastatic breast cancer (MBC) and progressive brain metastases. Despite assumptions that monoclonal antibodies do not cross the blood–brain barrier, molecular imaging shows localization of trastuzumab to brain metastases. Furthermore, preclinical data support dose-dependent activity of trastuzumab in intracranial tumor models. The PATRICIA study evaluated safety and efficacy of pertuzumab plus high-dose trastuzumab in patients with HER2+ MBC with central nervous system (CNS) metastases and CNS progression after radiation therapy (RT).1 At SABCS, results were presented from the primary efficacy analysis of PATRICIA.2
PATRICIA was a US-based, phase 2, open-label, single-arm study that included patients who had measurable (≥10 mm) CNS disease that had progressed after CNS-directed RT, in the setting of stable extracranial disease. Patients received pertuzumab (840-mg loading dose, then 420 mg every 3 weeks) and high-dose trastuzumab (6 mg/kg weekly), which continued until progression (CNS or systemic) or unacceptable toxicity. Patients could continue their existing systemic anti-cancer therapy during the study, with the exception of trastuzumab emtansine or lapatinib. The primary efficacy end point was confirmed objective response rate (ORR) in the CNS per Response Assessment in Neuro-Oncology Brain Metastases criteria. Secondary end points included duration of response (DOR), clinical benefit rate (CBR) in the CNS, and safety.
A total of 40 patients were enrolled across 16 sites; at the data cutoff (May 1, 2019), of 39 treated patients, 2 remained on study treatment and 37 discontinued treatment, most commonly due to CNS progression (n = 27). Median treatment duration was 4.5 months. Four patients in the efficacy population (n = 37) experienced a confirmed partial response, leading to an ORR of 11%. Median DOR was 4.6 months. The CBR (complete response + partial response + stable disease [SD] of ≥4 or ≥6 months) was 68% (SD ≥4 months) and 51% (SD ≥6 months). The adverse event profile was similar to that previously reported for pertuzumab and trastuzumab, with no new safety signals. No grade 5 adverse events were reported. The authors concluded that the CNS ORR of 11%, ≥6-month CBR of 51%, and lack of any new safety signals suggest that pertuzumab plus high-dose trastuzumab may have clinical utility in some patients with HER2+ MBC with progressive CNS metastases.
References
- Lin NU, et al. ASCO 2017. Abstract 2074.
- Lin NU, et al. SABCS 2019. Abstract P1-18-03.