Phase III Trial of Cisplatin Plus Gemcitabine With Either Placebo or Bevacizumab As First-Line Therapy for Nonsquamous Non-Small-Cell Lung Cancer: AVAiL Export

@article{citeulike:5206102, abstract = {PurposeBevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, improves survival when combined with carboplatin/paclitaxel for advanced nonsquamous non-small-cell lung cancer (NSCLC). This randomized phase III trial investigated the efficacy and safety of cisplatin/gemcitabine (CG) plus bevacizumab in this setting. Patients and MethodsPatients were randomly assigned to receive cisplatin 80 mg/m2 and gemcitabine 1,250 mg/m2 for up to six cycles plus low-dose bevacizumab (7.5 mg/kg), high-dose bevacizumab (15 mg/kg), or placebo every 3 weeks until disease progression. The trial was not powered to compare the two doses directly. The primary end point was amended from overall survival (OS) to progression-free survival (PFS). Between February 2005 and August 2006, 1,043 patients were randomly assigned (placebo, n = 347; low dose, n = 345; high dose, n = 351). ResultsPFS was significantly prolonged; the hazard ratios for PFS were 0.75 (median PFS, 6.7 v 6.1 months for placebo; P = .003) in the low-dose group and 0.82 (median PFS, 6.5 v 6.1 months for placebo; P = .03) in the high-dose group compared with placebo. Objective response rates were 20.1\%, 34.1\%, and 30.4\% for placebo, low-dose bevacizumab, and high-dose bevacizumab plus CG, respectively. Duration of follow-up was not sufficient for OS analysis. Incidence of grade 3 or greater adverse events was similar across arms. Grade [\≥] 3 pulmonary hemorrhage rates were [\≤] 1.5\% for all arms despite 9\% of patients receiving therapeutic anticoagulation. ConclusionCombining bevacizumab (7.5 or 15 mg/kg) with CG significantly improved PFS and objective response rate. Bevacizumab plus platinum-based chemotherapy offers clinical benefit for bevacizumab-eligible patients with advanced NSCLC. 10.1200/JCO.2007.14.5466}, author = {Reck, Martin and von Pawel, Joachim and Zatloukal, Petr and Ramlau, Rodryg and Gorbounova, Vera and Hirsh, Vera and Leighl, Natasha and Mezger, Jorg and Archer, Venice and Moore, Nicola and Manegold, Christian}, citeulike-article-id = {5206102}, citeulike-linkout-0 = {http://dx.doi.org/10.1200/JCO.2007.14.5466}, citeulike-linkout-1 = {http://jco.ascopubs.org/cgi/content/abstract/27/8/1227}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19188680}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19188680}, day = {10}, doi = {10.1200/JCO.2007.14.5466}, journal = {J Clin Oncol}, keywords = {nsclc}, month = {March}, number = {8}, pages = {1227--1234}, posted-at = {2009-07-20 03:56:33}, priority = {2}, title = {Phase III Trial of Cisplatin Plus Gemcitabine With Either Placebo or Bevacizumab As First-Line Therapy for Nonsquamous Non-Small-Cell Lung Cancer: AVAiL}, url = {http://dx.doi.org/10.1200/JCO.2007.14.5466}, volume = {27}, year = {2009} }

TY - JOUR ID - citeulike:5206102 L3 - citeulike-article-id:5206102 N2 - PurposeBevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, improves survival when combined with carboplatin/paclitaxel for advanced nonsquamous non-small-cell lung cancer (NSCLC). This randomized phase III trial investigated the efficacy and safety of cisplatin/gemcitabine (CG) plus bevacizumab in this setting. Patients and MethodsPatients were randomly assigned to receive cisplatin 80 mg/m2 and gemcitabine 1,250 mg/m2 for up to six cycles plus low-dose bevacizumab (7.5 mg/kg), high-dose bevacizumab (15 mg/kg), or placebo every 3 weeks until disease progression. The trial was not powered to compare the two doses directly. The primary end point was amended from overall survival (OS) to progression-free survival (PFS). Between February 2005 and August 2006, 1,043 patients were randomly assigned (placebo, n = 347; low dose, n = 345; high dose, n = 351). ResultsPFS was significantly prolonged; the hazard ratios for PFS were 0.75 (median PFS, 6.7 v 6.1 months for placebo; P = .003) in the low-dose group and 0.82 (median PFS, 6.5 v 6.1 months for placebo; P = .03) in the high-dose group compared with placebo. Objective response rates were 20.1%, 34.1%, and 30.4% for placebo, low-dose bevacizumab, and high-dose bevacizumab plus CG, respectively. Duration of follow-up was not sufficient for OS analysis. Incidence of grade 3 or greater adverse events was similar across arms. Grade [≥] 3 pulmonary hemorrhage rates were [≤] 1.5% for all arms despite 9% of patients receiving therapeutic anticoagulation. ConclusionCombining bevacizumab (7.5 or 15 mg/kg) with CG significantly improved PFS and objective response rate. Bevacizumab plus platinum-based chemotherapy offers clinical benefit for bevacizumab-eligible patients with advanced NSCLC. 10.1200/JCO.2007.14.5466 IS - 8 JF - J Clin Oncol EP - 1234 TI - Phase III Trial of Cisplatin Plus Gemcitabine With Either Placebo or Bevacizumab As First-Line Therapy for Nonsquamous Non-Small-Cell Lung Cancer: AVAiL VL - 27 SP - 1227 KW - nsclc AU - Reck, Martin AU - von Pawel, Joachim AU - Zatloukal, Petr AU - Ramlau, Rodryg AU - Gorbounova, Vera AU - Hirsh, Vera AU - Leighl, Natasha AU - Mezger, Jorg AU - Archer, Venice AU - Moore, Nicola AU - Manegold, Christian PY - 2009/03/10/ UR - http://dx.doi.org/10.1200/JCO.2007.14.5466 ER -