Jeffrey Crawford1, Paul Swanson, Paul Schwarzenberger, Alan Sandler, Diane Prager, Kathy Zhang, Daniel J Freeman, Carol W Johnson, Kartik Krishnan, David Johnson. 1. *Department of Medicine, Duke University Medical Center, Durham, North Carolina; †Hematology Oncology Associates, Port St. Lucie, Florida; ‡Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana; §Oregon Health and Science University, Portland, Oregon; ‖Illinois CancerCare, Peoria, Illinois; ¶Departments of Global Biostatistical Science, Oncology Research, and Global Safety, Amgen Inc., Thousand Oaks, California; and #Division of Hematology and Medical Oncology, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.
Abstract
INTRODUCTION: This two-part phase 2 study evaluated the efficacy and safety of panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody, combined with carboplatin/paclitaxel in patients with previously untreated advanced non-small-cell lung cancer. METHODS: In part 1, patients were sequentially enrolled to receive paclitaxel 200 mg/m(2) and carboplatin (area under the concentration-versus-time curve, 6 mg/min/ml) plus panitumumab (1.0, 2.0, or 2.5 mg/kg). In part 2, patients were randomized 2:1 to receive paclitaxel/carboplatin with (arm A) or without (arm B) the maximum tolerated dose of panitumumab identified in part 1. Primary endpoints in parts 1 and 2 were the incidence of dose-limiting toxicities and time to progression (TTP), respectively. RESULTS: In part 1, four of 19 patients had dose-limiting toxicities: three at 2.0 mg/kg (fatigue, pain in extremity, dyspepsia) and one at 2.5 mg/kg (rash). The maximum tolerated dose was not reached; panitumumab 2.5 mg/kg was selected for part 2. In part 2, TTP was 18.1 weeks (95% confidence interval [CI], 13.6-23.3) in arm A and 23.0 weeks (95% CI, 15.9-24.1) in arm B (hazard ratio, 0.9; 90% CI, 0.66-1.21; p = 0.555). Progression-free survival in arms A and B was 17.6 weeks and 18.3 weeks, respectively, and the objective response rate was 15.2% and 11.1%. Adverse events occurring more frequently in arm A than in arm B included skin toxicity, diarrhea, stomatitis, vomiting, and dizziness. Exploratory analyses did not demonstrate associations between potential biomarkers and outcomes. CONCLUSION: Although toxicity was predictable and manageable, the addition of panitumumab to paclitaxel/carboplatin did not improve TTP in patients with previously untreated advanced non-small-cell lung cancer.
RCT Entities:
INTRODUCTION: This two-part phase 2 study evaluated the efficacy and safety of panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody, combined with carboplatin/paclitaxel in patients with previously untreated advanced non-small-cell lung cancer. METHODS: In part 1, patients were sequentially enrolled to receive paclitaxel 200 mg/m(2) and carboplatin (area under the concentration-versus-time curve, 6 mg/min/ml) plus panitumumab (1.0, 2.0, or 2.5 mg/kg). In part 2, patients were randomized 2:1 to receive paclitaxel/carboplatin with (arm A) or without (arm B) the maximum tolerated dose of panitumumab identified in part 1. Primary endpoints in parts 1 and 2 were the incidence of dose-limiting toxicities and time to progression (TTP), respectively. RESULTS: In part 1, four of 19 patients had dose-limiting toxicities: three at 2.0 mg/kg (fatigue, pain in extremity, dyspepsia) and one at 2.5 mg/kg (rash). The maximum tolerated dose was not reached; panitumumab 2.5 mg/kg was selected for part 2. In part 2, TTP was 18.1 weeks (95% confidence interval [CI], 13.6-23.3) in arm A and 23.0 weeks (95% CI, 15.9-24.1) in arm B (hazard ratio, 0.9; 90% CI, 0.66-1.21; p = 0.555). Progression-free survival in arms A and B was 17.6 weeks and 18.3 weeks, respectively, and the objective response rate was 15.2% and 11.1%. Adverse events occurring more frequently in arm A than in arm B included skin toxicity, diarrhea, stomatitis, vomiting, and dizziness. Exploratory analyses did not demonstrate associations between potential biomarkers and outcomes. CONCLUSION: Although toxicity was predictable and manageable, the addition of panitumumab to paclitaxel/carboplatin did not improve TTP in patients with previously untreated advanced non-small-cell lung cancer.
Authors: S Cowherd; L D Miller; S A Melin; S Akman; S Isom; J Cole; A Pullikuth; J A Lawrence Journal: Cancer Biol Ther Date: 2015 Impact factor: 4.742