Add-on ipatasertib in maintenance setting a promising strategy in PIK3CA-mutated breast cancer

Adding ipatasertib to dual anti-HER2 maintenance therapy appears to be safe and beneficial to patients with HER2-positive metastatic breast cancer harbouring PIK3CA mutations, according to a phase Ib study.

A total of 17 patients with unresectable locally advanced or metastatic PIK3CA-mutated, HER2-positive breast cancer who had completed first-line induction chemotherapy plus trastuzumab and pertuzumab participated in the study. These patients received maintenance treatment with ipatasertib in combination with trastuzumab and pertuzumab.

The primary endpoint was maximum tolerated dose, defined as ipatasertib at 400 mg daily (21 days on and 7 days off) with standard trastuzumab and pertuzumab. This was established as the recommended phase II dosage, based on the absence of dose-limiting toxicities in the first six patients treated at this dosage during the initial 28-day cycle.

Seven patients (41.2 percent) had grade 3 treatment-related adverse events (TRAEs), the most common of which were diarrhoea and nausea. Two patients (11.8 percent) experienced serious TRAEs (diarrhoea, vomiting, ischaemic stroke, and pneumonitis) related to ipatasertib, from which they recovered.

Over a median follow-up of 27.7 months, the confirmed overall response rate was 31.1 percent (95 percent confidence interval [CI], 12.1–58.5), with a clinical benefit rate of 84.6 percent (95 percent CI, 53.7–97.3). The median progression-free survival was 16.4 months, with 47.3 percent of patients being free of progression at 18 months.