A phase II study evaluating the safety and efficacy of sunitinib with weekly paclitaxel followed by doxorubicin and daily oral cyclophosphamide plus G-CSF as neoadjuvant chemotherapy (NC) for locally advanced (LABC) or inflammatory breast cancer (IBC).
1090 Background: Sunitinib (S) is an oral tyrosine kinase inhibitor with anti-tumor and anti-angiogenic activity. The primary objective of this trial was to assess the pathologic complete response rate (pCR) in patients (pts) treated with NC consisting of S with weekly paclitaxel (T) followed by doxorubicin and daily oral cyclophosphamide plus G-CSF (AC+G-CSF). Correlative studies including circulating biomarkers are reported separately. Methods: Pts with HER2 negative LABC or IBC were eligible for this multicenter, phase II trial. Pts received S 25 mg po daily with T 80 mg/m2 IV Qweek (wk) x 12 wks, then AC+G-CSF (doxorubicin 24 mg/m2 IV Qwk + oral cyclophosphamide 60 mg/m2po daily + G-CSF 5 mcg/kg SC days 2-7) x 15 wks. pCR in the breast and axilla was assessed at surgery, and the MDACC CPS+EG score (validated score combining clinical and pathologic results for predicting survival in the neoadjuvant setting) was calculated. Results: 70 pts (ages 33-79) were enrolled; 68 received protocol therapy. 37 (53%) had ER and/or PR positive tumors. 2 patients were unevaluable (hypersensitivity to T, toxicity possibly related to S) and 3 withdrew consent prior to surgery. 61 pts reported any grade AE in S+P period. Among grade 3 or 4 AEs, neutropenia was most common in S+P period occurring in 31/68 (46%). pCR in the breast was observed in 27% (17/63, 95% CI 17%-40%) and breast and axilla in 15/63 (24%). In pts with ER positive tumors, pCR rate in breast was 8/34 (24%) and 9/29 (31%) for pts with ER negative tumors. 18 evaluable pts (29%) had CPS+EG scores ≤2, 40 (63%) had CPS+EG scores of ≥3, and 5 had insufficient information to calculate the CPS+EG score. When response was defined as pCR and/or CPS+EG score ≤ 2, 28 pts (44%) were responders. Conclusions: NC with T+S followed by AC+G-CSF was well tolerated. Using a combined definition of response of pCR and/or CPS+EG score ≤2, 28/63 (44%) pts had response; 19/34 (56%) for ER positive and 9/29 (31%) for ER negative disease. The addition of S to NC may result in promising incremental benefit for pts with ER positive breast cancer. Clinical trial information: NCT00513695.