Dasatinib in advanced HER2/neu amplified and ER/PR-positive breast cancer: Phase II study CA180088

1011 Background: SRC family kinases (SFKs) are involved in numerous signaling pathways including from ER and HER-2 receptors, as well as osteoclast function. Dasatinib is a potent oral inhibitor of SFKs. A phase II trial was performed in patients (pts) with ER+ and/or PR+ and/or HER-2-amplified progressive advanced breast cancer. Subsequent to study initiation, dasatinib demonstrated similar efficacy with a lower incidence of key side-effects at 100 mg once daily in CML and prostate cancer. Methods: Pts with measurable disease and progression after chemotherapy and other targeted agents were treated with dasatinib on a continuous twice-daily (BID) schedule; RECIST-defined response rate was primary endpoint. Results: Sixty-eight pts, 24 with HER-2-amplified and 44 with HER-2-normal, ER+ and/or PR+ disease, were treated. Original starting dose of 100 mg BID (23 pts) was reduced to 70 mg BID (45 pts) due to fluid retention, fatigue, or GI toxicity. Median age was 55 years; nearly all pts (93%) had prior ther...