Pertuzumab plus high-dose trastuzumab shows promise for selected patients with HER2-positive MBC

Treatment with pertuzumab plus high-dose trastuzumab appears to confer survival benefits in patients with HER2-positive metastatic breast cancer (MBC) with progressive central nervous system (CNS) metastases following radiotherapy, according to the phase II PATRICIA study.

In PATRICIA, 40 patients (median age 48 years, 90.0 percent White) were enrolled and assigned to receive intravenous pertuzumab (840 mg loading dose, then 420 mg once every 3-week cycle) plus intravenous high-dose trastuzumab (6 mg/kg weekly) until CNS or systemic PD, unacceptable toxicity, withdrawal, or study termination. A total of 39 patients received the study medications and 12 completed treatment.

Of the patients, 24 (60.0 percent) had extracranial disease and 11 (27.5 percent) were receiving concomitant systemic treatment for MBC. The median time from brain metastasis diagnosis until study entry was 19.4 months. Everyone had received radiotherapy, and the median time from last CNS-directed radiotherapy was 18.6 months.

The primary endpoint of confirmed objective response rate (ORR) per Response Assessment in Neuro-Oncology Brain Metastases criteria was 11 percent (95 percent CI, 3.0–25.4). The median progression-free survival (PFS)-CNS or systemic PFS was 4.6 months (95 percent CI, 4.0–8.9), and the median overall survival was 27.2 months (95 percent CI, 16.1–not reached).

At 6 months, the clinical benefit rate in the CNS was 51 percent (95 percent CI, 34.4–68.1). Two patients remained on treatment until study closure, and they achieved stable disease for 4.1 and 4.8 years, respectively.

In terms of safety, treatment-related grade 3/4 adverse events occurred in 7.7 percent of patients. Those with confirmed partial response or stable disease (≥4 months) in the CNS had stable patient-reported outcomes over time.