Hope S Rugo1, William T Barry2, Alvaro Moreno-Aspitia2, Alan P Lyss2, Constance Cirrincione2, Eleanor Leung2, Erica L Mayer2, Michael Naughton2, Deborah Toppmeyer2, Lisa A Carey2, Edith A Perez2, Clifford Hudis2, Eric P Winer2. 1. Hope S. Rugo, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; William T. Barry, Alliance Statistics and Data Center, Dana-Farber Cancer Institute; Erica L. Mayer and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Alvaro Moreno-Aspitia and Edith A. Perez, Mayo Clinic, Jacksonville, FL; Alan P. Lyss, Heartland Cancer Research Community Clinical Oncology Program; Michael Naughton, Washington University School of Medicine, St Louis, MO; Constance Cirrincione and Eleanor Leung, Alliance Statistics and Data Center, Duke University, Durham; Lisa A. Carey, University of North Carolina, Chapel Hill, NC; Deborah Toppmeyer, Cancer Institute of New Jersey, New Brunswick, NJ; and Clifford Hudis, Memorial Sloan Kettering Cancer Center, New York, NY. hrugo@medicine.ucsf.edu. 2. Hope S. Rugo, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; William T. Barry, Alliance Statistics and Data Center, Dana-Farber Cancer Institute; Erica L. Mayer and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Alvaro Moreno-Aspitia and Edith A. Perez, Mayo Clinic, Jacksonville, FL; Alan P. Lyss, Heartland Cancer Research Community Clinical Oncology Program; Michael Naughton, Washington University School of Medicine, St Louis, MO; Constance Cirrincione and Eleanor Leung, Alliance Statistics and Data Center, Duke University, Durham; Lisa A. Carey, University of North Carolina, Chapel Hill, NC; Deborah Toppmeyer, Cancer Institute of New Jersey, New Brunswick, NJ; and Clifford Hudis, Memorial Sloan Kettering Cancer Center, New York, NY.
Abstract
PURPOSE: We compared nab-paclitaxel or ixabepilone once per week to paclitaxel with bevacizumab as first-line therapy for patients with advanced breast cancer (BC) to evaluate progression-free survival (PFS) for nab-paclitaxel or ixabepilone versus paclitaxel. PATIENTS AND METHODS: Eligible patients were age ≥ 18 years with chemotherapy-naive advanced BC. Patients were randomly assigned to bevacizumab with paclitaxel 90 mg/m(2) (arm A), nab-paclitaxel 150 mg/m(2) (arm B), or ixabepilone 16 mg/m(2) (arm C), once per week for 3 of 4 weeks. Planned enrollment was 900 patients, which would give 88% power to detect a hazard ratio of 0.73. RESULTS: In all, 799 patients were enrolled, and 783 received treatment (97% receivedbevacizumab). Arm C was closed for futility at the first interim analysis (n = 241), and arm A (n = 267) and arm B (n = 275) were closed for futility at the second interim analysis. Median PFS for paclitaxel was 11 months, ixabepilone was inferior to paclitaxel (PFS, 7.4 months; hazard ratio, 1.59; 95% CI, 1.31 to 1.93; P < .001), and nab-paclitaxel was not superior to paclitaxel (PFS, 9.3 months; hazard ratio, 1.20; 95% CI, 1.00 to 1.45; P = .054). Results were concordant with overall survival; time to treatment failure was significantly shorter in both experimental arms v paclitaxel. Hematologic and nonhematologic toxicity, including peripheral neuropathy, was increased with nab-paclitaxel, with more frequent and earlier dose reductions. CONCLUSION: In patients with chemotherapy-naive advanced BC, ixabepilone once per week was inferior to paclitaxel, and nab-paclitaxel was not superior with a trend toward inferiority. Toxicity was increased in the experimental arms, particularly for nab-paclitaxel. Paclitaxel once per week remains the preferred palliative chemotherapy in this setting.
RCT Entities:
PURPOSE: We compared nab-paclitaxel or ixabepilone once per week to paclitaxel with bevacizumab as first-line therapy for patients with advanced breast cancer (BC) to evaluate progression-free survival (PFS) for nab-paclitaxel or ixabepilone versus paclitaxel. PATIENTS AND METHODS: Eligible patients were age ≥ 18 years with chemotherapy-naive advanced BC. Patients were randomly assigned to bevacizumab with paclitaxel 90 mg/m(2) (arm A), nab-paclitaxel 150 mg/m(2) (arm B), or ixabepilone 16 mg/m(2) (arm C), once per week for 3 of 4 weeks. Planned enrollment was 900 patients, which would give 88% power to detect a hazard ratio of 0.73. RESULTS: In all, 799 patients were enrolled, and 783 received treatment (97% received bevacizumab). Arm C was closed for futility at the first interim analysis (n = 241), and arm A (n = 267) and arm B (n = 275) were closed for futility at the second interim analysis. Median PFS for paclitaxel was 11 months, ixabepilone was inferior to paclitaxel (PFS, 7.4 months; hazard ratio, 1.59; 95% CI, 1.31 to 1.93; P < .001), and nab-paclitaxel was not superior to paclitaxel (PFS, 9.3 months; hazard ratio, 1.20; 95% CI, 1.00 to 1.45; P = .054). Results were concordant with overall survival; time to treatment failure was significantly shorter in both experimental arms v paclitaxel. Hematologic and nonhematologic toxicity, including peripheral neuropathy, was increased with nab-paclitaxel, with more frequent and earlier dose reductions. CONCLUSION: In patients with chemotherapy-naive advanced BC, ixabepilone once per week was inferior to paclitaxel, and nab-paclitaxel was not superior with a trend toward inferiority. Toxicity was increased in the experimental arms, particularly for nab-paclitaxel. Paclitaxel once per week remains the preferred palliative chemotherapy in this setting.
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Authors: Shaheenah Dawood; Kristine Broglio; Ana M Gonzalez-Angulo; Aman U Buzdar; Gabriel N Hortobagyi; Sharon H Giordano Journal: J Clin Oncol Date: 2008-08-25 Impact factor: 44.544
Authors: Hope S Rugo; Mario Campone; Dino Amadori; Daniela Aldrighetti; Pierfranco Conte; Andrew Wardley; Cristian Villanueva; Michelle Melisko; M Brent McHenry; David Liu; Francis Lee; Xavier Pivot Journal: Breast Cancer Res Treat Date: 2013-05-07 Impact factor: 4.872
Authors: Álvaro de Mingo Pulido; Alycia Gardner; Shandi Hiebler; Hatem Soliman; Hope S Rugo; Matthew F Krummel; Lisa M Coussens; Brian Ruffell Journal: Cancer Cell Date: 2018-01-08 Impact factor: 31.743
Authors: Mark Jesus M Magbanua; Hope S Rugo; Denise M Wolf; Louai Hauranieh; Ritu Roy; Praveen Pendyala; Eduardo V Sosa; Janet H Scott; Jin Sun Lee; Brandelyn Pitcher; Terry Hyslop; William T Barry; Steven J Isakoff; Maura Dickler; Laura Van't Veer; John W Park Journal: Clin Cancer Res Date: 2018-01-08 Impact factor: 12.531
Authors: Shailly Mehrotra; Manish R Sharma; Elizabeth Gray; Kehua Wu; William T Barry; Clifford Hudis; Eric P Winer; Alan P Lyss; Deborah L Toppmeyer; Alvaro Moreno-Aspitia; Thomas E Lad; Mario Valasco; Beth Overmoyer; Hope Rugo; Mark J Ratain; Jogarao V Gobburu Journal: AAPS J Date: 2017-06-15 Impact factor: 4.009
Authors: Marco Sisignano; Carlo Angioni; Chul-Kyu Park; Sascha Meyer Dos Santos; Holger Jordan; Maria Kuzikov; Di Liu; Sebastian Zinn; Stephan W Hohman; Yannick Schreiber; Béla Zimmer; Mike Schmidt; Ruirui Lu; Jing Suo; Dong-Dong Zhang; Stephan M G Schäfer; Martine Hofmann; Ajay S Yekkirala; Natasja de Bruin; Michael J Parnham; Clifford J Woolf; Ru-Rong Ji; Klaus Scholich; Gerd Geisslinger Journal: Proc Natl Acad Sci U S A Date: 2016-10-17 Impact factor: 11.205