TY - JOUR
T1 - A phase 2 randomized trial of paclitaxel and carboplatin with or without panitumumab for first-line treatment of advanced non-small-cell lung cancer
AU - Crawford, Jeffrey
AU - Swanson, Paul
AU - Schwarzenberger, Paul
AU - Sandler, Alan
AU - Prager, Diane
AU - Zhang, Kathy
AU - Freeman, Daniel J.
AU - Johnson, Carol W.
AU - Krishnan, Kartik
AU - Johnson, David
N1 - Funding Information:
The authors thank Benjamin Scott, PhD, and Ali Hassan, PhD (Complete Healthcare Communications, Inc., Chadds Ford, Pennsylvania), whose work was funded by Amgen Inc., Thousand Oaks, California, for assistance in writing this article.
Funding Information:
Disclosure: Dr. Jeffrey Crawford has served on advisory boards for Amgen Inc., Thousand Oaks, California; his institution has received a grant from Amgen Inc. for this study and has received research funding from Amgen Inc. Dr. Alan Sandler has served as consultant to and received honoraria from and travel expenses paid by Amgen Inc. Drs. Kathy Zhang and Carol W. Johnson are employees of and own stock in Amgen Inc. Drs. Kartik Krishnan and Daniel J. Freeman were employees of and owned stock in Amgen Inc. at the time the research was conducted. Drs. Paul Swanson, Paul Schwarzenberger, Diane Prager, and David Johnson declare no conflict of interest.
PY - 2013
Y1 - 2013
N2 - 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/m2 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 identifed 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.
AB - 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/m2 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 identifed 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.
KW - Epidermal growth factor receptor
KW - KRAS
KW - Non-small-cell lung cancer
KW - Paclitaxel/carboplatin
KW - Panitumumab
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U2 - 10.1097/JTO.0b013e3182a7d1da
DO - 10.1097/JTO.0b013e3182a7d1da
M3 - Article
C2 - 24389433
AN - SCOPUS:84892148005
SN - 1556-0864
VL - 8
SP - 1510
EP - 1518
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 12
ER -