title: Erlotinib and bevacizumab versus cisplatin, gemcitabine and bevacizumab in unselected nonsquamous nonsmall cell lung cancer.
abstract: Erlotinib with bevacizumab showed promising activity in recurrent nonsquamous (NS) nonsmall cell lung cancer (NSCLC). The INNOVATIONS study was designed to assess in first-line treatment of unselected cisplatin-eligible patients this combination compared to cisplatin, gemcitabine and bevacizumab. Stage IIIB/IV patients with NS-NSCLC were randomised on erlotinib (150 mg daily) and bevacizumab (15 mg·kg(-1) on day 1, every 3 weeks) (EB) until progression, or cisplatin (80 mg·m(-2) on day 1, every 3 weeks) and gemcitabine (1250 mg·m(-2) on days 1 and 8, every 3 weeks) up to six cycles and bevacizumab (15 mg·kg(-1) on day 1, every 3 weeks) (PGB) until progression. 224 patients were randomised (EB n=111, PGB n=113). The response rate (12% versus 36%; p<0.0001), progression-free survival (median 3.5 versus 6.9 months; hazard ratio (HR) 1.85, 95% CI 1.39-2.45; p<0.0001) and overall survival (median 12.6 versus 17.8 months; HR 1.41, 95% CI 1.01-1.97; p=0.04) clearly favoured PGB. In patients with epidermal growth factor receptor mutations (n=32), response rate, progression-free survival and overall survival were not superior with EB. Platinum-based combination chemotherapy remains the standard of care in first-line treatment of unselected NS-NSCLC. Molecular targeted approaches strongly mandate appropriate testing and patient selection.
authors: Dept of Thoracic Oncology, Thoraxklinik, Thoraxklinik im Universitätsklinikum Heidelberg, Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany michael.thomas@med.uni-heidelberg.de.
authors: Michael
authors: M
authors: Thomas
authors: Med. Clinic II, Oncology, Klinik Löwenstein, Löwenstein, Germany.
authors: Jürgen
authors: J
authors: Fischer
authors: Lungenfachklinik Immenhausen, Immenhausen, Germany Dept of Pneumology, Universitätsmedizin Göttingen, Göttingen, Germany.
authors: Stefan
authors: S
authors: Andreas
authors: Pneumology, Katholisches Klinikum Mainz, Mainz, Germany.
authors: Cornelius
authors: C
authors: Kortsik
authors: Pneumology and Lung Cancer Center, Gemeinschaftskrankenhaus Havelhöhe, Berlin, Germany.
authors: Christian
authors: C
authors: Grah
authors: Pneumology/Oncology, Lungenklinik Hemer, Hemer, Germany.
authors: Monika
authors: M
authors: Serke
authors: Malteser Krankenhaus St Hildegardis, Internal Medicine, Cologne, Germany.
authors: Michael
authors: M
authors: von Eiff
authors: Dept of Pneumological Oncology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Christian
authors: C
authors: Witt
authors: Lungenklinik Heckershorn, HELIOS Klinikum Emil von Behring, Berlin, Germany.
authors: Jens
authors: J
authors: Kollmeier
authors: Forschungszentrum Borstel, Medizinische Klinik, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Borstel, Germany.
authors: Ernst
authors: E
authors: Müller
authors: Krankenhaus Barmherzige Brüder Regensburg, Clinic for Oncology and Hematology, Regensburg, Germany.
authors: Michael
authors: M
authors: Schenk
authors: Hematology/Oncology, HELIOS St Johannes Klinik, Duisburg, Germany.
authors: Michael
authors: M
authors: Schröder
authors: Dept of Thoracic Oncology, Thoraxklinik, Thoraxklinik im Universitätsklinikum Heidelberg, Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany.
authors: Matthias
authors: M
authors: Villalobos
authors: Dept of Thoracic Oncology, Thoraxklinik, Thoraxklinik im Universitätsklinikum Heidelberg, Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany Lungenclinic Großhansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Großhansdorf, Germany.
authors: Niels
authors: N
authors: Reinmuth
authors: Dept of Pathology, University of Heidelberg, Heidelberg, Germany.
authors: Roland
authors: R
authors: Penzel
authors: Dept of Pathology, University of Heidelberg, Heidelberg, Germany.
authors: Philipp
authors: P
authors: Schnabel
authors: Coordinating Center for Clinical Trials, University of Marburg, Marburg, Germany.
authors: Thomas
authors: T
authors: Acker
authors: Coordinating Center for Clinical Trials, University of Marburg, Marburg, Germany.
authors: Alexander
authors: A
authors: Reuss
authors: Med. Clinic IV, Hematology/Oncology, Klinikum Kassel, Kassel, Germany.
authors: Martin
authors: M
authors: Wolf
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage*; D004252:DNA Mutational Analysis; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018450:Disease Progression; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D002945:Cisplatin; D000093542:Gemcitabine