Brian Leyland-Jones1, Igor Bondarenko2, Gia Nemsadze2, Vitaliy Smirnov2, Iryna Litvin2, Irakli Kokhreidze2, Lia Abshilava2, Mikheil Janjalia2, Rubi Li2, Kuntegowda C Lakshmaiah2, Beka Samkharadze2, Oksana Tarasova2, Ranjan Kumar Mohapatra2, Yaroslav Sparyk2, Sergey Polenkov2, Vladimir Vladimirov2, Liang Xiu2, Eugene Zhu2, Bruce Kimelblatt2, Kris Deprince2, Ilya Safonov2, Peter Bowers2, Els Vercammen2. 1. Brian Leyland-Jones, Avera Cancer Institute, Sioux Falls, SD; Igor Bondarenko, Dnepropetrovsk Medical Academy; and Iryna Litvin, Dnepropetrovsk Regional Oncological Dispensary, Dnepropetrovsk; Vitaliy Smirnov, Donetsk Regional Anticancer Center, Donetsk; Oksana Tarasova, Institute of Medical Radiology, Kharkiv; Yaroslav Sparyk, Lviv State Oncology Regional Treatment and Diagnostic Centre, Lviv; and Sergey Polenkov, Chernigov Regional Oncology Center, Chernigov, Ukraine; Gia Nemsadze, Institute of Clinical Oncology (LTD. K. Madichi Mammological Center); Irakli Kokhreidze, Martin D. Abeloff Laboratory Cancer Research Center; Lia Abshilava, Chemotherapy and Immunotherapy Clinic Medulla; Mikheil Janjalia, Tbilisi Cancer Center; and Beka Samkharadze, Research Institute of Clinical Medicine, Tbilisi, Georgia; Rubi Li, St. Luke's Medical Center, Quezon City, Philippines; Kuntegowda C. Lakshmaiah, Kidwai Memorial Institute of Oncology, Bangalore; and Ranjan Kumar Mohapatra, Apollo Specialty Hospital, Chennai, India; Vladimir Vladimirov, Pyatigorsk Oncology Dispensary, Pyatigorsk, Russian Federation; and Liang Xiu, Eugene Zhu, Bruce Kimelblatt, Kris Deprince, Ilya Safonov, Peter Bowers, and Els Vercammen, Janssen Research & Development, Raritan, NJ. bleylandj@aol.com. 2. Brian Leyland-Jones, Avera Cancer Institute, Sioux Falls, SD; Igor Bondarenko, Dnepropetrovsk Medical Academy; and Iryna Litvin, Dnepropetrovsk Regional Oncological Dispensary, Dnepropetrovsk; Vitaliy Smirnov, Donetsk Regional Anticancer Center, Donetsk; Oksana Tarasova, Institute of Medical Radiology, Kharkiv; Yaroslav Sparyk, Lviv State Oncology Regional Treatment and Diagnostic Centre, Lviv; and Sergey Polenkov, Chernigov Regional Oncology Center, Chernigov, Ukraine; Gia Nemsadze, Institute of Clinical Oncology (LTD. K. Madichi Mammological Center); Irakli Kokhreidze, Martin D. Abeloff Laboratory Cancer Research Center; Lia Abshilava, Chemotherapy and Immunotherapy Clinic Medulla; Mikheil Janjalia, Tbilisi Cancer Center; and Beka Samkharadze, Research Institute of Clinical Medicine, Tbilisi, Georgia; Rubi Li, St. Luke's Medical Center, Quezon City, Philippines; Kuntegowda C. Lakshmaiah, Kidwai Memorial Institute of Oncology, Bangalore; and Ranjan Kumar Mohapatra, Apollo Specialty Hospital, Chennai, India; Vladimir Vladimirov, Pyatigorsk Oncology Dispensary, Pyatigorsk, Russian Federation; and Liang Xiu, Eugene Zhu, Bruce Kimelblatt, Kris Deprince, Ilya Safonov, Peter Bowers, and Els Vercammen, Janssen Research & Development, Raritan, NJ.
Abstract
PURPOSE: An open-label, noninferiority study to evaluate the impact of epoetin alfa (EPO) on tumor outcomes when used to treat anemia in patients receiving chemotherapy for metastatic breast cancer. METHODS:Women with hemoglobin ≤ 11.0 g/dL, receiving first- or second-line chemotherapy for metastatic breast cancer, were randomly assigned to EPO 40,000 IU subcutaneously once a week or best standard of care. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, time to tumor progression, overall response rate, RBC transfusions, and thrombotic vascular events. RESULTS: In 2,098 patients randomly assigned, median PFS (based on investigator-determined disease progression [PD]) was 7.4 months in both groups (hazard ratio [HR], 1.089; 95% CI, 0.988 to 1.200); upper bound exceeded prespecified noninferiority margin of 1.15. Median PFS per independent review committee-determined PD was 7.6 months in both groups (HR, 1.028; 95% CI, 0.922 to 1.146); upper bound did not exceed prespecified noninferiority margin. Median overall survival at clinical cutoff (1,337 deaths) was 17.2 months in the EPO and 17.4 months in the best standard of care group (HR, 1.057; 95% CI, 0.949 to 1.177), median time to tumor progression was 7.5 months in both groups (HR, 1.094; 95% CI, 0.991 to 1.209), and overall response rate was 50% versus 51% (odds ratio, 0.950; 95% CI, 0.799 to 1.130). RBC transfusions were 5.8% versus 11.4% (P < .001), and thrombotic vascular events were 2.8% versus 1.4% (P = .038), respectively. CONCLUSION: The primary end point, PFS based on investigator-determined PD, did not meet noninferiority criteria. As a consistency assessment with the primary finding, PFS based on independent review committee-determined PD met noninferiority criteria. Overall, this study did not achieve noninferiority objective in ruling out a 15% increased risk in PD/death. RBC transfusion should be the preferred approach for the management of anemia in this population.
RCT Entities:
PURPOSE: An open-label, noninferiority study to evaluate the impact of epoetin alfa (EPO) on tumor outcomes when used to treat anemia in patients receiving chemotherapy for metastatic breast cancer. METHODS:Women with hemoglobin ≤ 11.0 g/dL, receiving first- or second-line chemotherapy for metastatic breast cancer, were randomly assigned to EPO 40,000 IU subcutaneously once a week or best standard of care. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, time to tumor progression, overall response rate, RBC transfusions, and thrombotic vascular events. RESULTS: In 2,098 patients randomly assigned, median PFS (based on investigator-determined disease progression [PD]) was 7.4 months in both groups (hazard ratio [HR], 1.089; 95% CI, 0.988 to 1.200); upper bound exceeded prespecified noninferiority margin of 1.15. Median PFS per independent review committee-determined PD was 7.6 months in both groups (HR, 1.028; 95% CI, 0.922 to 1.146); upper bound did not exceed prespecified noninferiority margin. Median overall survival at clinical cutoff (1,337 deaths) was 17.2 months in the EPO and 17.4 months in the best standard of care group (HR, 1.057; 95% CI, 0.949 to 1.177), median time to tumor progression was 7.5 months in both groups (HR, 1.094; 95% CI, 0.991 to 1.209), and overall response rate was 50% versus 51% (odds ratio, 0.950; 95% CI, 0.799 to 1.130). RBC transfusions were 5.8% versus 11.4% (P < .001), and thrombotic vascular events were 2.8% versus 1.4% (P = .038), respectively. CONCLUSION: The primary end point, PFS based on investigator-determined PD, did not meet noninferiority criteria. As a consistency assessment with the primary finding, PFS based on independent review committee-determined PD met noninferiority criteria. Overall, this study did not achieve noninferiority objective in ruling out a 15% increased risk in PD/death. RBC transfusion should be the preferred approach for the management of anemia in this population.
Authors: Richard E Kast; Nicolas Skuli; Samuel Cos; Georg Karpel-Massler; Yusuke Shiozawa; Ran Goshen; Marc-Eric Halatsch Journal: Breast Cancer (Dove Med Press) Date: 2017-07-11