Preliminary results of a phase I study of sunitinib plus paclitaxel for first-line treatment of advanced breast cancer

C196 Background Sunitinib malate is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, RET, and FLT3, with single-agent activity in patients (pts) with previously-treated metastatic breast cancer (BC). This phase I study investigated the safety and pharmacokinetics (PK) of sunitinib combined with paclitaxel for first-line treatment of advanced BC.
 Materials and methods Eligible pts had metastatic or locally recurrent BC, ECOG PS ≤1, and adequate organ function. Exclusion criteria included prior cytotoxic therapy for advanced disease and failure of taxane-based adjuvant therapy within 12 months. Pts received sunitinib at a starting dose of 25 mg/day continuous dosing (escalation to 37.5 mg/day or reduction to 12.5 mg/day depending on tolerability) plus paclitaxel 1-hr infusion 90 mg/m 2 /wk in 4-wk cycles (3 wks on treatment, followed by 1 wk off; reduction to 65 mg/m 2 /wk as needed). Results 21 pts were treated with the combination regimen on study, median age 58 yrs (range 37-74). 18 pts had measurable disease, and 6 pts were chemotherapy-naive. Approximately 50% of patients were hormone-receptor positive and 5% were positive for HER2 receptor overexpression. Disease sites included bone (57%), liver (38%), lung (33%), and lymph node (57%). Median number of cycles delivered was 7 (range 2-15) for sunitinib and 5 (range 1[[Unsupported Character - Codename s]]-14) for paclitaxel. Discontinuations were due to disease progression (13 pts), maximum response (2 pts), completed study (4 pts), withdrawn consent (1 pt), and adverse event (AE; chronic leg ulcer, 1 pt). Grade (Gr) 3 AEs included fatigue (27%), diarrhea (14%), hand-foot syndrome (9%), dyspepsia (9%), and dyspnea (9%). Neutropenia was the primary hematologic toxicity (Gr 3 in 33% and Gr 4 in 19%). G-CSF was used when neutrophil count was Conclusions Sunitinib administered with paclitaxel was generally well tolerated and showed promising activity as first-line treatment for advanced BC. A phase III trial comparing this combination to paclitaxel + bevacizumab is underway.