Background: S is an oral, small molecule, multi-targeted tyrosine kinase inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, stem cell factor receptor, and colony-stimulating factor-1 receptor with demonstrated single agent activity in multiple tumor types including breast cancer. S's anti-proliferative and anti-angiogenic activity stimulated interest in combining it with a variety of chemotherapy regimens. In the previously reported Phase I portion of this trial, S 25mg PO daily was determined feasible in combination with weekly P and C, an active regimen for TNBC. We now report the feasibility and efficacy of the phase II evaluation of this combination as neoadjuvant therapy with pathologic complete response (pCR) as the primary endpoint.

Methods: Eligibility criteria included: invasive adenocarcinoma, triple negative histology defined as ER/ PR negative (<10% IHC staining) as well as HER2-negative (IHC 0–1+ or FISH neg), clinical T1-3, N0-1, M0 with clinical N3, T4 and T1 N0 M0 tumors excluded, ECOG PS 0–2, normal LVEF, and adequate organ function. All pts received P 70mg/m2 (Days 1, 8, 15) + C AUC=5 (Day 1) with S 25mg PO daily q 28 days for 6 cycles. Response assessments were performed after 3 cycles, and in the absence of disease progression or unacceptable toxicity, study treatment continued for 3 additional cycles. Postoperatively, pts resumed S 25 mg qd until 52 weeks from D1. Definition of pCR was an absence of invasive cancer in both breast and lymph nodes. A pCR rate of ≥ 30% would warrant additional evaluation of this regimen.

Results: The phase II portion of this trial enrolled 36 pts from 2/2011 to present. This analysis is based on 22 pts evaluable for toxicity and efficacy. Median tumor size was 4 cm with 68% designated T2 and 27% as T3 and 63% with clinical N1 or N2 disease. A median of 3 preoperative cycles was delivered. Best clinical response was; cCR − 1 (5%), cPR − 9 (41%), cSD − 6 (27%), PD − 1 (5%), UE − 5 (22%). Pathologic responses are as follows: ypCR −2 pts (9%), PR2 (residual invasive cancer in breast, negative lymph nodes −1 pt, PR3 (residual invasive cancer in breast and lymph nodes) −1 pt. 3 pts of the 4 with surgical outcomes completed all 6 cycles of treatment; 2 of which had pCR. Poor tolerance/toxicity resulted in 8 pts proceeding to surgery early/or discontinuation and 2 pts experienced progression; data is pending in 8 pts. Grade 3/4 hematologic toxicity consisted of neutropenia-15 pts (68%) with fever in 2 (9%), anemia −9 pts (41%), and thrombocytopenia-8 pts (36%). No G3/4 non-hematologic toxicity was present in >5% of pts.

Conclusions: The addition of sunitinib to paclitaxel and carboplatin was accompanied by significant hematologic toxicity resulting in the inability to deliver the planned study therapy. Treatment discontinuations were frequent as was the need for dose adjustments and modifications. The sunitinib-paclitaxel/carboplatin combination evaluated in this study is not recommended for further use in locally advanced breast cancer.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-14.