Véronique Diéras1,2, Hervé Bonnefoi3, Emilio Alba4, Ahmad Awada5, Bruno Coudert6, Xavier Pivot7, Joseph Gligorov8, Agnes Jager9, Stefania Zambelli10, Geoffrey J Lindeman11, Eric Charpentier12, Gary T Emmons13, Ignacio Garcia-Ribas14, Robert Paridaens15, Jaap Verweij9. 1. Department of Medical Oncology, Institut Curie, Paris, France. v.dieras@rennes.unicancer.fr. 2. Centre Eugène Marquis, Avenue de la bataille Flandres-Dunkerque, CS 44229, 35042, Rennes Cedex, France. v.dieras@rennes.unicancer.fr. 3. Institut Bergonié, Univ. Bordeaux, INSERM U1218, INSERM CIC1401, Bordeaux, France. 4. Department of Clinical Oncology, Hospital Clínico Universitario Virgen de la Victoria, Málaga, Spain. 5. Oncology Medicine Department, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. 6. Medical Oncology Department, Centre Georges François Leclerc, Dijon, France. 7. Department of Medical Oncology, Centre Paul Strauss, Strasbourg, France. 8. Medical Oncology Dept Tenon Hospital, Inserm U938, Institut Universitaire de Cancérologie APHP-Sorbonne Université, Paris, France. 9. Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. 10. Department of Medical Oncology, IRCCS OSR, San Raffaele, Milan, Italy. 11. Department of Medical Oncology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia. 12. Statistics Department, Sanofi, 640 Memorial Drive, Cambridge, MA, 02139, USA. 13. Translational Medicine and Early Development, Sanofi, Bridgewater, NJ, USA. 14. Early Oncology Development, Sanofi, Madrid, Spain. 15. Department of Medical Oncology, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium.
Abstract
PURPOSE:Metastatic triple-negative breast cancer (TNBC) is a phenotypic breast cancer subgroup with a very poor prognosis, despite standard treatments. Combined twice-weekly iniparib and gemcitabine/carboplatin (GC+tw-iniparib) showed benefit over gemcitabine/carboplatin in a randomized phase II trial, and a phase III was initiated comparing these regimens. The present phase II study was initiated to compare GC+tw-iniparib with a more practical once-weekly schedule (GC+w-iniparib) in TNBC. METHODS:Metastatic TNBC patients were randomized to receive iniparib weekly (11.2 mg/kg on days 1 and 8) or twice-weekly (5.6 mg/kg on days 1, 4, 8, and 11) with gemcitabine (1000 mg/m2) and carboplatin (area under the curve 2 on days 1 and 8), every 3 weeks. The primary endpoint was the overall response rate (ORR). Pharmacokinetics of iniparib and its two metabolites were analyzed. RESULTS:A total of 163 patients were randomized, 82 GC+w-iniparib and 81 GC+tw-iniparib. Demographic and baseline characteristics were well balanced. ORR was 34.1% (95% CI 23.9-44.4%) vs. 29.6% (95% CI 19.7-39.6%) and median progression-free survival was 5.5 months (95% CI 4.2-5.7) vs. 4.3 months (95% CI 3.0-5.8) for GC+w-iniparib and GC+tw-iniparib, respectively. Safety was similar across treatment arms in terms of event severity and type. Iniparib plasma concentrations and exposure were two-fold higher with w-iniparib compared to tw-iniparib. Iniparib and its metabolites were cleared rapidly with a terminal half-life of < 1 h, without accumulation. CONCLUSIONS: Despite a doubled maximum concentration with weekly iniparib, no detectable differences in safety or efficacy were observed between the weekly and twice-weekly administration schedules in this population. TRIAL REGISTRATION: ClinicalTrial.gov Identifier NCT01045304.
RCT Entities:
PURPOSE: Metastatic triple-negative breast cancer (TNBC) is a phenotypic breast cancer subgroup with a very poor prognosis, despite standard treatments. Combined twice-weekly iniparib and gemcitabine/carboplatin (GC+tw-iniparib) showed benefit over gemcitabine/carboplatin in a randomized phase II trial, and a phase III was initiated comparing these regimens. The present phase II study was initiated to compare GC+tw-iniparib with a more practical once-weekly schedule (GC+w-iniparib) in TNBC. METHODS: Metastatic TNBC patients were randomized to receive iniparib weekly (11.2 mg/kg on days 1 and 8) or twice-weekly (5.6 mg/kg on days 1, 4, 8, and 11) with gemcitabine (1000 mg/m2) and carboplatin (area under the curve 2 on days 1 and 8), every 3 weeks. The primary endpoint was the overall response rate (ORR). Pharmacokinetics of iniparib and its two metabolites were analyzed. RESULTS: A total of 163 patients were randomized, 82 GC+w-iniparib and 81 GC+tw-iniparib. Demographic and baseline characteristics were well balanced. ORR was 34.1% (95% CI 23.9-44.4%) vs. 29.6% (95% CI 19.7-39.6%) and median progression-free survival was 5.5 months (95% CI 4.2-5.7) vs. 4.3 months (95% CI 3.0-5.8) for GC+w-iniparib and GC+tw-iniparib, respectively. Safety was similar across treatment arms in terms of event severity and type. Iniparib plasma concentrations and exposure were two-fold higher with w-iniparib compared to tw-iniparib. Iniparib and its metabolites were cleared rapidly with a terminal half-life of < 1 h, without accumulation. CONCLUSIONS: Despite a doubled maximum concentration with weekly iniparib, no detectable differences in safety or efficacy were observed between the weekly and twice-weekly administration schedules in this population. TRIAL REGISTRATION: ClinicalTrial.gov Identifier NCT01045304.
Entities:
Keywords:
Administration schedule; Iniparib; Metastatic triple-negative breast cancer; Pharmacokinetics
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