Multicenter phase 1b trial of addition of ipatasertib to dual anti-HER2 maintenance therapy in PIK3CA-mutated HER2-positive metastatic breast cancer

The multicenter phase 1b SOLTI-1507 IPATHER trial in Spain evaluated safety and feasibility of ipatasertib (AKT inhibitor) combined with trastuzumab and pertuzumab (HP), with or without endocrine therapy, as maintenance therapy after first-line treatment in patients with HER2-positive metastatic breast cancer (mBC) harboring PIK3CA mutations. Seventeen patients were enrolled, with a median follow-up of 27.7 months. During the dose-selection phase, ipatasertib 400 mg daily (21 days on and 7 days off) with standard HP was established as the recommended phase 2 dose, based on the absence of dose-limiting toxicities in the first six patients treated with this dose during the initial 28-day cycle (primary endpoint). Grade 3 treatment-related adverse events occurred in seven patients (41.2%), most commonly diarrhea and nausea. The confirmed overall response rate was 31.1% (95% CI 12.1-58.5) with clinical benefit rate 84.6% (53.7-97.3) and median progression-free survival 16.4 months (9.4-NR). PFS rate at 18 months was 47.3%. The authors conclude that these results support ipatasertib plus HP as a safe and promising maintenance strategy for HER2-positive mBC harboring PIK3CA mutations.