breast cancer

Pertuzumab Plus High-Dose Trastuzumab in Patients With Progressive Brain Metastases and HER2-Positive Metastatic Breast Cancer: Primary Analysis of a Phase II Study

In the August 20, 2021 addition of JCO Nancy Lin and colleagues published on the results of pertuzumab plus high-dose trastuzumab in patients with progressive brain metastases and HER-2/neu positive metastatic breast cancer. Given the paucity of efficacious therapies in this patient population, investigators wanted to test the hypothesis that there is a dose-dependent response to trastuzumab based off of xenograft models.

The phase II PATRICIA study involved patients with HER-2/neu-positive metastatic breast cancer with central nervous system metastases and CNS progression despite prior radiotherapy. Patients received pertuzumab plus high-dose trastuzumab (6 mg/kg weekly) until there was central nervous system or systemic progression or intolerable toxicity. The primary end point was confirmed ORR in the CNS per Response Assessment in Neuro-Oncology Brain Metastases criteria. Secondary end points included DoR, clinical benefit rate (CR + PR + SD ≥ 4 or ≥ 6 months) in the CNS, as well as safety.

39 patients were treated for a median of 4.5 (0.3-37.3) months data cutoff. 37 patients discontinued treatment, most commonly because of CNS progression (n = 27); 2 patients remained on treatment per investigators. CNS overall response rate was 11% (95% CI, 3 to 25), with four partial responses (median duration of response, 4.6 months). The documented clinical benefit rate at 4 months and 6 months was 68% and 51%, respectively. 2 patients permanently discontinued study treatment because of significant adverse events (treatment-related left ventricular dysfunction and seizure, both grade 3). No grade 5 adverse events were reported. No new safety signals emerged with either agent.

The authors concluded “although the CNS ORR was modest, 68% of patients experienced clinical benefit, and two patients had ongoing stable intracranial and extracranial disease for > 2 years. High-dose trastuzumab for HER2-positive CNS metastases may warrant further study.”