A Phase I-Ii Study Of Dasatinib (D) In Combination With Weekly (W) Paclitaxel (P) For Patients (Pts) With Metastatic Breast Carcinoma (Mbc)

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 D 150mg C2 and came off study. 1 pt developed G3 febrile neutropenia on D 150mg C2 and withdrew. Overall the most common Rx-related toxicities have been hematologic and low G (Table). 7 of 12 (58%) pts treated with D ≥100mg had diarrhea (3pts; G1, 4pts; G2). 3 pts developed edema (all G1, D≥120mg). 12 pts are evaluable for response; 3pts (25%) PR (2 prior taxane, progressed C7, 1 continues on C10), 4 pts (33%) SD. Conclusions: Treatment with wP and D is feasible in pts with MBC. 1 DLT occurred at D 150 mg but due to cumulative toxicities the phase II dose is 120 mg. Preliminary evidence of activity has been seen in taxane-pretreated pts. Pts with SRC+ tumors, or active SRC signaling could be more sensitive to this approach. AE Total N (%) G1 N (%) G2 N (%) G3 N (%) G4 N (%) ↑Glucose 15 (100) 7 (47) 8 (53) - - ↑ QTc 13 (87) 9 (60) 4 (27) - - ↑AST 11 (73) 9 (60) 2 (13) - - ↓Hb 11 (73) 8 (53) 2 (13) 1 (7) - ↓Leukocytes 11 (74) 7 (47) 3 (20) 1 (7) - Neuropathy 11 (73) 8 (53) 2 (13) 1 (7%) - Fatigue 10 (67) 6 (40) 2 (13) 2 (13) - ↓Albumin 8 (53) 7 (47) 1 (7) - - ↑ALT 8 (53) 6 (40) 2 (13) - - Skin toxicity 8 (53) 6 (40) 2 (13) - - Nausea 7 (47) 5 (33) 2 (13) - - ↓Phosphate 7 (47) 0 5 (33) 2 (13) - ↓Platelets 6 (40) 4 (27) 1 (7) 1 (7) - ↓Neutrophils 5 (33) 0 4 (27) 1 (7) - ↑Alk phos 4 (27) 3 (20) - 1 (7) - ↑Sodium 4 (27) 4 (27) - - - Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb