Denise A Yardley1,2, Edward R Arrowsmith3,4, Brooke R Daniel3,4, Janice Eakle3,5, Adam Brufsky6, David R Drosick3,7, Fred Kudrik3,8, Linda D Bosserman9, Mark R Keaton10, Sharon A Goble11, Jeffrey A Bubis12, Victor M Priego13, Kelly Pendergrass14, Yvonne Manalo15, Martin Bury16, Donald S Gravenor17, Gladys I Rodriguez18, Roger C Inhorn19, Robyn R Young3,20, William N Harwin3,5, Caryn Silver3,5, John D Hainsworth3,21, Howard A Burris3,21. 1. Sarah Cannon Research Institute, 250 25th Avenue North, Suite 100, Nashville, TN, 37203, USA. dyardley@tnonc.com. 2. Tennessee Oncology, Nashville, TN, USA. dyardley@tnonc.com. 3. Sarah Cannon Research Institute, 250 25th Avenue North, Suite 100, Nashville, TN, 37203, USA. 4. Tennessee Oncology, Chattanooga, TN, USA. 5. Florida Cancer Specialists, Fort Meyers, FL, USA. 6. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. 7. Oncology Hematology Care, Cincinnati, OH, USA. 8. South Carolina Oncology Associates, Columbia, SC, USA. 9. Wilshire Oncology Medical Group, La Verne, CA, USA. 10. Augusta Oncology Associates, Augusta, GA, USA. 11. Virginia Cancer Institute, Richmond, VA, USA. 12. ICON/Cancer Specialists of North Florida, Jacksonville, FL, USA. 13. Center for Cancer and Blood Disorder, Bethesda, MD, USA. 14. Kansas City Cancer Center, Overland Park, KS, USA. 15. Costal Bend Cancer Center, Corpus Christi, TX, USA. 16. Cancer Research Consortium of West Michigan, Grand Rapids, MI, USA. 17. Family Cancer Center, Memphis, TN, USA. 18. South Texas Oncology Hematology, San Antonio, TX, USA. 19. Mercy Hospital, Portland, ME, USA. 20. The Center for Cancer and Blood Disorders, Ft Worth, TX, USA. 21. Tennessee Oncology, Nashville, TN, USA.
Abstract
PURPOSE:Ixabepilone is a microtubule stabilizer with activity in taxane-refractory metastatic breast cancer and low susceptibility to taxane-resistance mechanisms including multidrug-resistant phenotypes and high β-III tubulin expression. Since these resistance mechanisms are common in triple-negative breast cancer (TNBC), ixabepilone may have particular advantages in this patient population. This study evaluated the substitution of ixabepilone for paclitaxel following doxorubicin/cyclophosphamide (AC) in the adjuvant treatment of early-stage TNBC. METHODS:Patients with operable TNBC were eligible following definitive breast surgery. Patients were randomized (1:1) to receive four cycles of AC followed by either four cycles (12 weeks) of ixabepilone or 12 weekly doses of paclitaxel. RESULTS:614 patients were randomized: 306 toAC/ixabepilone and 308 to AC/paclitaxel. At a median follow-up of 48 months, 59 patients had relapsed (AC/ixabepilone, 29; AC/paclitaxel, 30). The median time from diagnosis to relapse was 20.8 months. The 5-year disease-free survival (DFS) rates of the two groups were similar [HR 0.92; ixabepilone 87.1% (95% CI 82.6-90.5) vs. paclitaxel 84.7% (95% CI 79.7-88.6)]. The estimated 5-year overall survival (OS) rates were also similar [HR 1.1; ixabepilone 89.7% (95% CI 85.5-92.7) vs. paclitaxel 89.6% (95% CI 85.0-92.9)]. Peripheral neuropathy was the most common grade 3/4 event. Dose reductions and treatment discontinuations occurred more frequently during paclitaxel treatment. CONCLUSIONS: Treatment with AC/ixabepilone provided similar DFS and OS in patients with operable TNBC when compared to treatment with AC/paclitaxel. The two regimens had similar toxicity, although treatment discontinuation, dose modifications, and overall peripheral neuropathy were more frequent with AC/paclitaxel. TRIAL REGISTRATION: Clinical Trials.gov Identifier, NCT00789581.
RCT Entities:
PURPOSE:Ixabepilone is a microtubule stabilizer with activity in taxane-refractory metastatic breast cancer and low susceptibility to taxane-resistance mechanisms including multidrug-resistant phenotypes and high β-III tubulin expression. Since these resistance mechanisms are common in triple-negative breast cancer (TNBC), ixabepilone may have particular advantages in this patient population. This study evaluated the substitution of ixabepilone for paclitaxel following doxorubicin/cyclophosphamide (AC) in the adjuvant treatment of early-stage TNBC. METHODS:Patients with operable TNBC were eligible following definitive breast surgery. Patients were randomized (1:1) to receive four cycles of AC followed by either four cycles (12 weeks) of ixabepilone or 12 weekly doses of paclitaxel. RESULTS: 614 patients were randomized: 306 to AC/ixabepilone and 308 to AC/paclitaxel. At a median follow-up of 48 months, 59 patients had relapsed (AC/ixabepilone, 29; AC/paclitaxel, 30). The median time from diagnosis to relapse was 20.8 months. The 5-year disease-free survival (DFS) rates of the two groups were similar [HR 0.92; ixabepilone 87.1% (95% CI 82.6-90.5) vs. paclitaxel 84.7% (95% CI 79.7-88.6)]. The estimated 5-year overall survival (OS) rates were also similar [HR 1.1; ixabepilone 89.7% (95% CI 85.5-92.7) vs. paclitaxel 89.6% (95% CI 85.0-92.9)]. Peripheral neuropathy was the most common grade 3/4 event. Dose reductions and treatment discontinuations occurred more frequently during paclitaxel treatment. CONCLUSIONS: Treatment with AC/ixabepilone provided similar DFS and OS in patients with operable TNBC when compared to treatment with AC/paclitaxel. The two regimens had similar toxicity, although treatment discontinuation, dose modifications, and overall peripheral neuropathy were more frequent with AC/paclitaxel. TRIAL REGISTRATION: Clinical Trials.gov Identifier, NCT00789581.
Entities:
Keywords:
Cyclophosphamide; Doxorubicin; Ixabepilone; Triple-negative breast cancer
Authors: Priyanka Sharma; Sara López-Tarruella; José Angel García-Saenz; Qamar J Khan; Henry L Gómez; Aleix Prat; Fernando Moreno; Yolanda Jerez-Gilarranz; Agustí Barnadas; Antoni C Picornell; María Del Monte-Millán; Milagros González-Rivera; Tatiana Massarrah; Beatriz Pelaez-Lorenzo; María Isabel Palomero; Ricardo González Del Val; Javier Cortés; Hugo Fuentes-Rivera; Denisse Bretel Morales; Iván Márquez-Rodas; Charles M Perou; Carolyn Lehn; Yen Y Wang; Jennifer R Klemp; Joshua V Mammen; Jamie L Wagner; Amanda L Amin; Anne P O'Dea; Jaimie Heldstab; Roy A Jensen; Bruce F Kimler; Andrew K Godwin; Miguel Martín Journal: Clin Cancer Res Date: 2018-07-30 Impact factor: 12.531
Authors: Melina L Willson; Lucinda Burke; Thomas Ferguson; Davina Ghersi; Anna K Nowak; Nicholas Wilcken Journal: Cochrane Database Syst Rev Date: 2019-09-02