Safety and pharmacokinetic study of the combination of trastuzumab emntansine and non-pegylated liposomal doxorubicin for the treatment of advanced her2 positive breast cancer

Resumen

This single-arm, open-label, multicenter, phase Ib study (NCT02562378) enrolled subjects with anthracycline-naïve HER2+ MBC that had progressed on trastuzumab and taxanes. A standard ¿3 plus 3¿ dose-escalation design was used, followed by a dose-expansion cohort. Patients received a maximum of 6 cycles of NPLD intravenously (IV) at various dose levels (45, 50, and 60 mg/m2) in the dose-escalation part and at 60 mg/m2 during expansion every 3 weeks (Q3W) plus standard doses of T-DM1. The primary endpoint was to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of this combination. A total of 15 patients were included (12 patients during the dose-escalation part and three additional patients in the dose-expansion cohort). One patient experienced a DLT at 60 mg/m2 dose level (grade 4 neutropenia lasting 13 days). The MTD was T-DM1 3.6 mg/kg plus NPLD 60 mg/m2 administered IV Q3W. No clinically relevant worsening of cardiac function was reported. Overall response rate was 40.0% with a median duration of response of 6.9 months, clinical benefit rate was 66.7%, and median progression-free survival was 7.2 months (95%CI, 4.5¿9.6). No significant influence of NPLD on T-DM1 pharmacokinetics was observed.