A phase Ib study of lapatinib plus pegylated liposomal doxorubicin in patients with advanced HER2-positive breast cancer.

600Background: Conventional anthracyclines are particularly active in HER2-positive breast cancer (BC), but their use concomitantly with anti-HER2 agents is limited by cardiotoxicity. Pegylated liposomal doxorubicin (PLD) and lapatinib (L) offer a safer alternative for combining these two classes of agents. Methods: This is an open label phase Ib study, with 3+3 dose escalation design. Patients with HER2-positive (FISH amplified or immunohistochemistry 3+) advanced BC, progressing after trastuzumab with a cumulative dose of doxorubicin ≤ 240 mg/m2 or equivalent, received PLD 30 mg/m2 intravenously on day 1 plus escalating doses of L orally on days 1-21 of each 21-day cycle (L dose levels 1 / 2: 1250 / 1500 mg/m2). The primary endpoint was to define the maximum tolerated dose (MTD) at first cycle, and secondary endpoints were the activity and safety profile with multiple cycles. Results: Nine patients out of 11 enrolled were evaluable (1 excluded for allergic reaction at first PLD dose, 1 withdrew consent)...