| J Clin Oncol. 2009 Feb 2. [Epub ahead of print] | Related Articles, LinkOut |
Phase III Trial of Cisplatin Plus Gemcitabine With Either Placebo or Bevacizumab As First-Line Therapy for Nonsquamous Non-Small-Cell Lung Cancer: AVAiL.
Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, Leighl N, Mezger J, Archer V, Moore N, Manegold C.
Krankenhaus Grosshansdorf, Grosshansdorf; Asklepios Fachkliniken München-Gauting, Muenchen-Gauting; St. Vincentius-Kliniken, Karlsruhe; Heidelberg University Medical Center, Mannheim, Germany; Third Faculty of Medicine, Charles University, Postgraduate Medical School, Prague, Czech Republic; Wielkopolskie Centrum Chorob Pluc i Gruzlicy, Poznan, Poland; Cancer Research Center, Moscow, Russia; McGill University Health Centre-Royal Victoria Hospital, Montreal, Quebec; Princess Margaret Hospital, Toronto, Ontario, Canada; and F. Hoffmann-La Roche Ltd, Basel, Switzerland.
PURPOSE: Bevacizumab, 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 METHODS: Patients were randomly assigned to receive cisplatin 80 mg/m(2) and gemcitabine 1,250 mg/m(2) 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). RESULTS: PFS 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