Joyce O'Shaughnessy1, Lee Schwartzberg2, Michael A Danso2, Kathy D Miller2, Hope S Rugo2, Marcus Neubauer2, Nicholas Robert2, Beth Hellerstedt2, Mansoor Saleh2, Paul Richards2, Jennifer M Specht2, Denise A Yardley2, Robert W Carlson2, Richard S Finn2, Eric Charpentier2, Ignacio Garcia-Ribas2, Eric P Winer2. 1. Joyce O'Shaughnessy, Baylor Charles A. Sammons Cancer Center, Texas Oncology; Joyce O'Shaughnessy, US Oncology, Dallas; Beth Hellerstedt Texas Oncology-Round Rock, Austin, TX; Lee Schwartzberg, Accelerated Community Oncology Research Network; Lee Schwartzberg, The West Clinic, Memphis; Denise A. Yardley, Sarah Cannon Research Institute; Denise A. Yardley, Tennessee Oncology, Nashville, TN; Michael A. Danso, US Oncology; Michael A. Danso, Virginia Oncology Associates, Norfolk; Nicholas Robert, Virginia Cancer Specialists, Fairfax; Paul Richards, Blue Ridge Cancer Care, Salem, VA; Kathy D. Miller, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN; Hope S. Rugo, University of California, San Francisco Comprehensive Cancer Center, San Francisco; Robert W. Carlson, Stanford Comprehensive Cancer Center, Palo Alto, CA; Richard S. Finn, Geffen School of Medicine at University of California, Los Angeles; Richard S. Finn, Translational Research in Oncology, Los Angeles, CA; Marcus Neubauer, Kansas City Cancer City, Overland Park, KS; Mansoor Saleh, Georgia Cancer Specialists, Sandy Springs, GA; Jennifer M. Specht, University of Washington, Seattle Cancer Care Alliance, Seattle, WA; Eric Charpentier, Ignacio Garcia-Ribas, Sanofi, Cambridge; and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA. joyce.oshaughnessy@usoncology.com. 2. Joyce O'Shaughnessy, Baylor Charles A. Sammons Cancer Center, Texas Oncology; Joyce O'Shaughnessy, US Oncology, Dallas; Beth Hellerstedt Texas Oncology-Round Rock, Austin, TX; Lee Schwartzberg, Accelerated Community Oncology Research Network; Lee Schwartzberg, The West Clinic, Memphis; Denise A. Yardley, Sarah Cannon Research Institute; Denise A. Yardley, Tennessee Oncology, Nashville, TN; Michael A. Danso, US Oncology; Michael A. Danso, Virginia Oncology Associates, Norfolk; Nicholas Robert, Virginia Cancer Specialists, Fairfax; Paul Richards, Blue Ridge Cancer Care, Salem, VA; Kathy D. Miller, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN; Hope S. Rugo, University of California, San Francisco Comprehensive Cancer Center, San Francisco; Robert W. Carlson, Stanford Comprehensive Cancer Center, Palo Alto, CA; Richard S. Finn, Geffen School of Medicine at University of California, Los Angeles; Richard S. Finn, Translational Research in Oncology, Los Angeles, CA; Marcus Neubauer, Kansas City Cancer City, Overland Park, KS; Mansoor Saleh, Georgia Cancer Specialists, Sandy Springs, GA; Jennifer M. Specht, University of Washington, Seattle Cancer Care Alliance, Seattle, WA; Eric Charpentier, Ignacio Garcia-Ribas, Sanofi, Cambridge; and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA.
Abstract
PURPOSE: There is a lack of treatments providing survival benefit for patients with metastatic triple-negative breast cancer (mTNBC), with no standard of care. A randomized phase II trial showed significant benefit for gemcitabine, carboplatin, and iniparib (GCI) over gemcitabine and carboplatin (GC) in clinical benefit rate, response rate, progression-free survival (PFS), and overall survival (OS). Here, we formally compare the efficacy of these regimens in a phase III trial. PATIENTS AND METHODS: Patients with stage IV/locally recurrent TNBC who had received no more than two previous chemotherapy regimens for mTNBC were randomly allocated to gemcitabine 1,000 mg/m(2) and carboplatin area under the curve 2 (days 1 and 8) alone or GC plus iniparib 5.6 mg/kg (days 1, 4, 8, and 11) every 3 weeks. Random assignment was stratified by the number of prior chemotherapies. The coprimary end points were OS and PFS. Patients receiving GC could cross over to iniparib on progression. RESULTS:Five hundred nineteen patients were randomly assigned (261 GCI; 258 GC). In the primary analysis, no statistically significant difference was observed for OS (hazard ratio [HR] = 0.88; 95% CI, 0.69 to 1.12; P = .28) nor PFS (HR = 0.79; 95% CI, 0.65 to 0.98; P = .027). An exploratory analysis showed that patients in the second-/third-line had improved OS (HR = 0.65; 95% CI, 0.46 to 0.91) and PFS (HR = 0.68; 95% CI, 0.50 to 0.92) with GCI. The safety profile for GCI was similar to GC. CONCLUSION: The trial did not meet the prespecified criteria for the coprimary end points of PFS and OS in the ITT population. The potential benefit with iniparib observed in second-/third-line subgroup warrants further evaluation.
RCT Entities:
PURPOSE: There is a lack of treatments providing survival benefit for patients with metastatic triple-negative breast cancer (mTNBC), with no standard of care. A randomized phase II trial showed significant benefit for gemcitabine, carboplatin, and iniparib (GCI) over gemcitabine and carboplatin (GC) in clinical benefit rate, response rate, progression-free survival (PFS), and overall survival (OS). Here, we formally compare the efficacy of these regimens in a phase III trial. PATIENTS AND METHODS: Patients with stage IV/locally recurrent TNBC who had received no more than two previous chemotherapy regimens for mTNBC were randomly allocated to gemcitabine 1,000 mg/m(2) and carboplatin area under the curve 2 (days 1 and 8) alone or GC plus iniparib 5.6 mg/kg (days 1, 4, 8, and 11) every 3 weeks. Random assignment was stratified by the number of prior chemotherapies. The coprimary end points were OS and PFS. Patients receiving GC could cross over to iniparib on progression. RESULTS: Five hundred nineteen patients were randomly assigned (261 GCI; 258 GC). In the primary analysis, no statistically significant difference was observed for OS (hazard ratio [HR] = 0.88; 95% CI, 0.69 to 1.12; P = .28) nor PFS (HR = 0.79; 95% CI, 0.65 to 0.98; P = .027). An exploratory analysis showed that patients in the second-/third-line had improved OS (HR = 0.65; 95% CI, 0.46 to 0.91) and PFS (HR = 0.68; 95% CI, 0.50 to 0.92) with GCI. The safety profile for GCI was similar to GC. CONCLUSION: The trial did not meet the prespecified criteria for the coprimary end points of PFS and OS in the ITT population. The potential benefit with iniparib observed in second-/third-line subgroup warrants further evaluation.
Authors: Narjust Duma; Kelly C Gast; Grace M Choong; Roberto A Leon-Ferre; Ciara C O'Sullivan Journal: Curr Oncol Rep Date: 2018-06-08 Impact factor: 5.075
Authors: Véronique Diéras; Hervé Bonnefoi; Emilio Alba; Ahmad Awada; Bruno Coudert; Xavier Pivot; Joseph Gligorov; Agnes Jager; Stefania Zambelli; Geoffrey J Lindeman; Eric Charpentier; Gary T Emmons; Ignacio Garcia-Ribas; Robert Paridaens; Jaap Verweij Journal: Breast Cancer Res Treat Date: 2019-06-06 Impact factor: 4.872
Authors: Susan E Bates; Donald A Berry; Sanjeeve Balasubramaniam; Stuart Bailey; Patricia M LoRusso; Eric H Rubin Journal: Clin Cancer Res Date: 2015-10-15 Impact factor: 12.531
Authors: Ana C Gregório; Manuela Lacerda; Paulo Figueiredo; Sérgio Simões; Sérgio Dias; João Nuno Moreira Journal: Pathol Oncol Res Date: 2017-09-14 Impact factor: 3.201
Authors: Eva Tonsing-Carter; Barbara J Bailey; M Reza Saadatzadeh; Jixin Ding; Haiyan Wang; Anthony L Sinn; Kacie M Peterman; Tiaishia K Spragins; Jayne M Silver; Alyssa A Sprouse; Taxiarchis M Georgiadis; T Zachary Gunter; Eric C Long; Robert E Minto; Christophe C Marchal; Christopher N Batuello; Ahmad R Safa; Helmut Hanenberg; Paul R Territo; George E Sandusky; Lindsey D Mayo; Christine M Eischen; Harlan E Shannon; Karen E Pollok Journal: Mol Cancer Ther Date: 2015-10-22 Impact factor: 6.261