Cynthia Osborne1, Jagathi D Challagalla2, Charles F Eisenbeis3, Frankie Ann Holmes4, Marcus A Neubauer5, Nicholas W Koutrelakos6, Carlos A Taboada7, Sasha J Vukelja8, Sharon T Wilks9, Mary Ann Allison10, Praveen Reddy2, Scot Sedlacek11, Yunfei Wang12, Lina Asmar12, Joyce O'Shaughnessy13. 1. US Oncology Research, McKesson Specialty Health, The Woodlands, TX; Texas Oncology, Baylor-Sammons Cancer Center, Dallas, TX. Electronic address: Cynthia.Osborne@USONCOLOGY.com. 2. US Oncology Research, McKesson Specialty Health, The Woodlands, TX; Texas Oncology, Wichita Falls, KS. 3. US Oncology Research, McKesson Specialty Health, The Woodlands, TX; Cancer Centers of North Carolina, Raleigh, NC. 4. US Oncology Research, McKesson Specialty Health, The Woodlands, TX; Texas Oncology-Houston Memorial City, Houston, TX. 5. US Oncology Research, McKesson Specialty Health, The Woodlands, TX; Kansas City Cancer Center-Southwest, Overland Park, KS. 6. US Oncology Research, McKesson Specialty Health, The Woodlands, TX; Maryland Oncology Hematology PA, Columbia, MD. 7. US Oncology Research, McKesson Specialty Health, The Woodlands, TX; Texas Oncology-Methodist Charlton Cancer Center, Dallas, TX. 8. US Oncology Research, McKesson Specialty Health, The Woodlands, TX; Texas Oncology-Tyler, Tyler, TX. 9. US Oncology Research, McKesson Specialty Health, The Woodlands, TX; Texas Oncology-San Antonio, San Antonio, TX. 10. US Oncology Research, McKesson Specialty Health, The Woodlands, TX; Comprehensive Cancer Centers of Nevada, Henderson, NV. 11. US Oncology Research, McKesson Specialty Health, The Woodlands, TX; Rocky Mountain Cancer Centers, Denver, CO. 12. US Oncology Research, McKesson Specialty Health, The Woodlands, TX. 13. US Oncology Research, McKesson Specialty Health, The Woodlands, TX; Texas Oncology, Baylor-Sammons Cancer Center, Dallas, TX.
Abstract
BACKGROUND: Hormonal therapies and single-agent sequential chemotherapeutic regimens are the standards of care for HER2- metastatic breast cancer (MBC). However, treating patients with hormone-refractory and triple negative (TN) MBC remains challenging. We report the results of combined ixabepilone and carboplatin in a single-arm phase II trial. PATIENTS AND METHODS: In the present prospective analysis of hormone receptor-positive (HR+)/HER2- and TN MBC cohorts, patients could have received 0 to 2 chemotherapy regimens for MBC before enrollment. All patients received ixabepilone 20 mg/m2 and carboplatin (area under the curve, 2.5) on days 1 and 8 every 21 days. The primary endpoint was the objective response rate (ORR). The secondary objectives included progression-free survival (PFS), clinical benefit rate (CBR), overall survival (OS), and toxicity. RESULTS: We enrolled 54 HR+ and 49 TN patients (median, 1 previous chemotherapy regimen for metastatic disease; most in addition to adjuvant chemotherapy). The ORR was 34% and 30.4% for the HR+ and TN patients, respectively, with a corresponding CBR of 56.6% and 41.3%. The ORRs were similar in taxane-pretreated patients (ORR, 31.4% and 28.6% for HR+ and TN patients, respectively). The median OS was 17.9 months for HR+ patients and 12.5 months for TN patients. The median PFS was similar for both groups at 7.6 months. Grade 3/4 nonhematologic toxicities included neuropathy (9%) and fatigue (8%). Nine patients developed grade 3/4 neuropathy, 7 of whom had received previous taxane treatment. CONCLUSION: Ixabepilone plus carboplatin is active even in later-line HR+ and TN disease. Toxicities were manageable without cumulative myelosuppression. This combination is a reasonable option for those patients with MBC who require combination chemotherapy.
BACKGROUND: Hormonal therapies and single-agent sequential chemotherapeutic regimens are the standards of care for HER2- metastatic breast cancer (MBC). However, treating patients with hormone-refractory and triple negative (TN) MBC remains challenging. We report the results of combined ixabepilone and carboplatin in a single-arm phase II trial. PATIENTS AND METHODS: In the present prospective analysis of hormone receptor-positive (HR+)/HER2- and TN MBC cohorts, patients could have received 0 to 2 chemotherapy regimens for MBC before enrollment. All patients received ixabepilone 20 mg/m2 and carboplatin (area under the curve, 2.5) on days 1 and 8 every 21 days. The primary endpoint was the objective response rate (ORR). The secondary objectives included progression-free survival (PFS), clinical benefit rate (CBR), overall survival (OS), and toxicity. RESULTS: We enrolled 54 HR+ and 49 TNpatients (median, 1 previous chemotherapy regimen for metastatic disease; most in addition to adjuvant chemotherapy). The ORR was 34% and 30.4% for the HR+ and TNpatients, respectively, with a corresponding CBR of 56.6% and 41.3%. The ORRs were similar in taxane-pretreated patients (ORR, 31.4% and 28.6% for HR+ and TNpatients, respectively). The median OS was 17.9 months for HR+ patients and 12.5 months for TNpatients. The median PFS was similar for both groups at 7.6 months. Grade 3/4 nonhematologic toxicities included neuropathy (9%) and fatigue (8%). Nine patients developed grade 3/4 neuropathy, 7 of whom had received previous taxane treatment. CONCLUSION:Ixabepilone plus carboplatin is active even in later-line HR+ and TN disease. Toxicities were manageable without cumulative myelosuppression. This combination is a reasonable option for those patients with MBC who require combination chemotherapy.