Denise A Yardley1, John D Zubkus2, Janice F Eakle3, Rebecca G Bechhold4, Lindsey Finney5, Davey Daniel6, Brooke Daniel6, John D Hainsworth2. 1. Sarah Cannon Research Institute, Nashville, TN; Tennessee Oncology, PLLC, Nashville, TN. Electronic address: dyardley@tnonc.com. 2. Sarah Cannon Research Institute, Nashville, TN; Tennessee Oncology, PLLC, Nashville, TN. 3. Florida Cancer Specialists, Fort Myers, FL. 4. Oncology Hematology Care, Cincinnati, OH. 5. Sarah Cannon Research Institute, Nashville, TN. 6. Sarah Cannon Research Institute, Nashville, TN; Tennessee Oncology, PLLC, Chattanooga, TN.
Abstract
BACKGROUND: Ixabepilone is a member of the epothilone class of antineoplastic agents with activity against taxane-resistant tumors, and low susceptibility to common mechanisms of tumor resistance. This study evaluated ixabepilone in lieu of a taxane in combination with carboplatin and trastuzumab as neoadjuvant treatment for operable HER2-positive breast cancer. PATIENTS AND METHODS: Patients ≥ 18 years of age with histologically-confirmed HER2-positive adenocarcinoma of the breast (clinical T1-T3, N0-N2, M0), normal left ventricular ejection fraction, and adequate organ function received trastuzumab 6 mg/kg intravenous (I.V.) (with 8 mg/kg loading dose cycle 1), ixabepilone 40 mg/m(2) I.V., and carboplatin area under the curve = 6.0 I.V. on day 1 of each 21-day cycle. Prophylactic growth factor support was permitted. After completing 6 cycles, patients underwent definitive surgery. After surgery, patients continued trastuzumab every 3 weeks for a total of 1 year. Locoregional radiation therapy and endocrine therapy was administered per institutional guidelines. The primary end point was the rate of pCR. RESULTS: Fifty-eight eligible women (median tumor size, 3.0 cm; clinical axillary lymph node involvement, 67%) initiated treatment between April 2009 and February 2010. Fifty-two patients (90%) underwent surgery, and pCR was observed in 27 patients (52%). Grade 3/4 neutropenia was the most common toxicity, occurring in 69% of patients and complicated by fever in 4 patients. CONCLUSION: The combination of ixabepilone, carboplatin, and trastuzumab was feasible and active as a neoadjuvant regimen. Although the pCR rate of 52% falls within the range reported with other taxane/trastuzumab-based regimens, the greater incidence of severe neutropenia is a disadvantage for this regimen.
BACKGROUND:Ixabepilone is a member of the epothilone class of antineoplastic agents with activity against taxane-resistant tumors, and low susceptibility to common mechanisms of tumor resistance. This study evaluated ixabepilone in lieu of a taxane in combination with carboplatin and trastuzumab as neoadjuvant treatment for operable HER2-positive breast cancer. PATIENTS AND METHODS: Patients ≥ 18 years of age with histologically-confirmed HER2-positive adenocarcinoma of the breast (clinical T1-T3, N0-N2, M0), normal left ventricular ejection fraction, and adequate organ function received trastuzumab 6 mg/kg intravenous (I.V.) (with 8 mg/kg loading dose cycle 1), ixabepilone 40 mg/m(2) I.V., and carboplatin area under the curve = 6.0 I.V. on day 1 of each 21-day cycle. Prophylactic growth factor support was permitted. After completing 6 cycles, patients underwent definitive surgery. After surgery, patients continued trastuzumab every 3 weeks for a total of 1 year. Locoregional radiation therapy and endocrine therapy was administered per institutional guidelines. The primary end point was the rate of pCR. RESULTS: Fifty-eight eligible women (median tumor size, 3.0 cm; clinical axillary lymph node involvement, 67%) initiated treatment between April 2009 and February 2010. Fifty-two patients (90%) underwent surgery, and pCR was observed in 27 patients (52%). Grade 3/4 neutropenia was the most common toxicity, occurring in 69% of patients and complicated by fever in 4 patients. CONCLUSION: The combination of ixabepilone, carboplatin, and trastuzumab was feasible and active as a neoadjuvant regimen. Although the pCR rate of 52% falls within the range reported with other taxane/trastuzumab-based regimens, the greater incidence of severe neutropenia is a disadvantage for this regimen.