title: Randomized phase II-III study of bevacizumab in combination with chemotherapy in previously untreated extensive small-cell lung cancer: results from the IFCT-0802 trial†.
abstract: BACKGROUND
  This randomized phase II-III trial sought to evaluate the efficacy and safety of adding bevacizumab (Bev) following induction chemotherapy (CT) in extensive small-cell lung cancer (SCLC).
  
  
  METHODS
  Enrolled SCLC patients received two induction cycles of CT. Responders were randomly assigned 1:1 to receive four additional cycles of CT alone or CT plus Bev (7.5 mg/kg), followed by single-agent Bev until progression or unacceptable toxicity. The primary end point was the percentage of patients for whom disease remained controlled (still in response) at the fourth cycle.
  
  
  RESULTS
  In total, 147 patients were enrolled. Partial response was observed in 103 patients, 74 of whom were eligible for Bev and randomly assigned to the CT alone group (n = 37) or the CT plus Bev group (n = 37). Response assessment at the end of the fourth cycle showed that disease control did not differ between the two groups (89.2% versus 91.9% of patients remaining responders in CT alone versus CT plus Bev, respectively; Fisher's exact test: P = 1.00). Progression-free survival (PFS) since randomization did not significantly differ, with a median PFS of 5.5 months [95% confidence interval (CI) 4.9% to 6.0%] versus 5.3 months (95% CI 4.8% to 5.8%) in the CT alone and CT plus Bev groups, respectively [hazard ratio (HR) for CT alone: 1.1; 95% CI 0.7% to 1.7%; unadjusted P = 0.82]. Grade ≥2 hypertension and grade ≥3 thrombotic events were observed in 40% and 11% of patients, respectively, in the CT plus Bev group. Serum vascular endothelial growth factor (VEGF) and soluble VEGF receptor titrations failed to identify predictive biomarkers.
  
  
  CONCLUSIONS
  Administering 7.5 mg/kg Bev after induction did not improve outcome in extensive SCLC patients.
authors: Pneumology Department, University Hospital, Montpellier. Electronic address: jl-pujol@chu-montpellier.fr.
authors: J-L
authors: JL
authors: Pujol
authors: Pneumology Department, AP-HP Hospital Tenon, Paris.
authors: A
authors: A
authors: Lavole
authors: Pneumology Department, University Hospital, Strasbourg.
authors: E
authors: E
authors: Quoix
authors: Respiratory Diseases Department, Le Mans Hospital, Le Mans.
authors: O
authors: O
authors: Molinier
authors: Pneumology Department, Pierre-Bénite Hospital, Lyon.
authors: P-J
authors: PJ
authors: Souquet
authors: Oncology Department, Hopital Nord, Aix-Marseille University.
authors: F
authors: F
authors: Barlesi
authors: Pneumology Department, Draguignan Hospital, Draguignan.
authors: H
authors: H
authors: Le Caer
authors: Pneumology Department, University Hospital, Grenoble.
authors: D
authors: D
authors: Moro-Sibilot
authors: Oncology Department, Loire Cancer Institute, St-Priest-en-Jarez.
authors: P
authors: P
authors: Fournel
authors: Pneumology Department, Colmar Hospital, Colmar.
authors: J P
authors: JP
authors: Oster
authors: Pneumology Department, Alpes-Léman Hospital, Ambilly.
authors: P
authors: P
authors: Chatellain
authors: Pneumology Department, Jean Rougier Hospital, Cahors.
authors: P
authors: P
authors: Barre
authors: Pneumology Department, Gabriel Montpied University Hospital, Clermont-Ferrand.
authors: G
authors: G
authors: Jeannin
authors: Pneumology Department, Private Hospital, Cornebarrieu.
authors: P
authors: P
authors: Mourlanette
authors: Pneumology Department, Private Hospital, Maubeuge.
authors: M
authors: M
authors: Derollez
authors: Pneumology Department, Nevers Hospital, Nevers.
authors: D
authors: D
authors: Herman
authors: Pneumology Department, Pau Hospital, Pau.
authors: A
authors: A
authors: Renault
authors: Pneumology Department, Saint-Quentin Hospital, Saint-Quentin.
authors: C
authors: C
authors: Dayen
authors: Department of Biopathology and Oncogenetics, Regional Cancer Institute, Montpellier.
authors: P J
authors: PJ
authors: Lamy
authors: French Cooperative Thoracic Intergroup (IFCT), Paris.
authors: A
authors: A
authors: Langlais
authors: French Cooperative Thoracic Intergroup (IFCT), Paris.
authors: F
authors: F
authors: Morin
authors: Pneumology Department, University Hospital, Caen, France.
authors: G
authors: G
authors: Zalcman
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D018450:Disease Progression; D018572:Disease-Free Survival; D015251:Epirubicin / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D005602:France; D006801:Humans; D060828:Induction Chemotherapy; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D000068258:Bevacizumab; D015251:Epirubicin; D005047:Etoposide; D003520:Cyclophosphamide; D002945:Cisplatin
keywords: anti-angiogenesis therapy; bevacizumab; chemotherapy; small-cell lung cancer