A pilot study of adjuvant doxorubicin and cyclophosphamide followed by paclitaxel plus sorafenib in women with node positive or high-risk breast cancer.

Abstract

Abstract Abstract #2110 Background: Targeting angiogenesis is an effective treatment strategy in many solid tumors including breast cancer (BC). Sorafenib is a small molecule inhibitor of angiogenesis and other tumor growth signaling. We conducted a pilot phase 2 trial incorporating sorafenib into standard adjuvant BC treatment. Material and Methods: The primary endpoint of this multicenter community-based study was to assess the safety of doxorubicin and cyclophosphamide followed by paclitaxel in combination with sorafenib in patients (pts) with node positive or otherwise high-risk BC. Eligibility criteria included: either mastectomy or breast conserving surgery-with axillary node assessment for stage I, II, IIIA, and IIIC (T1-3, N3a only) BC. Pts were either lymph node positive or high-risk node negative (tumor size >2 cm; hormone receptor negative; grade 2-3; or age <35 years). Additional inclusion criteria included: HER2-negative, ECOG performance status 0-1, normal left ventricular ejection fraction by echocardiography or MUGA scan, adequate organ function, and signed informed consent. Treatment consisted of doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2 (AC) both IV day 1 every 3 weeks x 4 cycles, followed by paclitaxel 175mg/m2 day 1 every 3 weeks x 4 cycles or 80mg/m2 IV weekly x 12, combined with sorafenib 400mg orally twice daily. Sorafenib was held during radiation therapy (where indicated) and resumed once completed. Sorafenib was continued for a total of 12 months and in combination with adjuvant hormonal therapy (where indicated.) LV assessments occurred after AC, paclitaxel, and every 3 months during maintenance sorafenib. Results: Forty-five pts were enrolled from 5/07 to 1/08. The median follow-up is 6 months (range 4-12 months). Baseline characteristics included: median age 54 years (35-74); ECOG 0, 93%; node positive, 80%; and hormone receptor negative 33%. Nineteen pts (42%) discontinued sorafenib before completing paclitaxel (mean time on sorafenib 3.7 weeks; <1 week in 18% of all pts). 9 of these 19 pts (47%) stopped sorafenib due to symptoms. Grade (G) 3/4 non-hematologic toxicity during sorafenib therapy in >5%: arthralgias/myalgias, neuropathy, pain, and pulmonary symptoms (8% each), and rash (11%). G3/4 hematologic toxicity during sorafenib treatment was limited to neutropenia in 11%. There were no sorafenib-related deaths. Discussion: In this pilot study, sorafenib was generally associated with limited severe toxicity when combined with paclitaxel following AC. However, many pts discontinued sorafenib early suggesting sequential scheduling may be more feasible than concurrent administration with chemotherapy. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2110.