According to a new study published in the journal Breast Cancer Research and Treatment, researchers have found that pilaralisib plus trastuzumab with or without paclitaxel have an acceptable safety profile in patients with trastuzumab-refractory human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.
Pilaralisib is a potent, selective PI3K inhibitor. For the phase 1/2 dose-escalation study, researchers enrolled 42 patients with trastuzumab-refractory metastatic HER2-positive breast cancer and assigned them to receive pilaralisib plus trastuzumab (Arm 1) or pilaralisib plus trastuzumab and paclitaxel (Arm 2). The starting dose of pilaralisib was 200mg once daily.
Results showed that five patients experienced dose-limiting toxicities, three of whom were in Arm 1. Three patients experienced dose-limiting rash and two had dose-limiting neutropenia.
Researchers determined the maximum tolerated dose of pilaralisib to be 400mg once daily. The common adverse events in both arms were diarrhea, fatigue, and rash, but incidence was lower in Arm 1.
The most common severe adverse events were erythematous rash in Arm 1 and peripheral neuropathy, diarrhea, and neutropenia in Arm 2. In regard to efficacy, no patients in Arm 1 achieved a response, but 20% of evaluable patients in Arm 2 achieve a partial response.
This phase I/II dose-escalation study investigated the maximum tolerated dose (MTD), safety, pharmacokinetics, and efficacy of the pan-class I phosphoinositide 3-kinase inhibitor pilaralisib in combination with trastuzumab (Arm 1) or trastuzumab plus paclitaxel (Arm 2) in patients with HER2-positive metastatic breast cancer.