Dasatinib (D) in combination with weekly (w) paclitaxel (P) for patients (pts) with metastatic breast carcinoma (MBC): A phase I/II study.

1156 Background: Inhibition of SRC is a novel approach for MBC. Preclinically, the SRC inhibitor D + P had superior antitumor activity to either agent alone. We designed this phase I-II study to translate this observation. Methods: For phase I: pts with MBC, ECOG PS 0-1, normal hepatic, renal, marrow function were eligible. Pts with pleural/pericardial effusions were excluded. For phase II: pts had measurable, HER2-negative MBC, ≤2 prior rx for MBC. Cycle (C) consisted of wP 80 mg/m2 IV 3/4 weeks + D 70mg orally daily; escalating to 100 mg, 120 mg, and 150 mg in cohorts of 3 pts. Toxicity was assessed by CTCAE v3.0, response by RECIST. Results: 15 pts (14 females, 1 male) enrolled; median age 54 (range 35-74), median PS=1 (range 0-1). 11 (73%) pts rcvd prior adjuvant chemoRx. Pts rcvd a median of 3 prior rx for MBC (range 0-12). Pts rcvd median of 2 C of D + P (range 1-10). One DLT occurred at 150 mg (G3 fatigue); this cohort was expanded with no further DLTs to date. However, 1 pt had a skin reaction to ...