title: Bevacizumab in Patients with Nonsquamous Non-Small Cell Lung Cancer and Asymptomatic, Untreated Brain Metastases (BRAIN): A Nonrandomized, Phase II Study.
abstract: OBJECTIVE
  The phase II prospective, noncomparative BRAIN study (NCT00800202) investigated efficacy and safety of bevacizumab in chemotherapy-naïve or pretreated patients with non-small cell lung cancer (NSCLC) and asymptomatic untreated brain metastases to provide data in this previously unexplored subgroup.
  
  
  METHODS
  Patients with stage IV nonsquamous NSCLC, Eastern Cooperative Oncology Group performance status 0-1, and untreated, asymptomatic brain metastases received first-line bevacizumab (15 mg/kg) plus carboplatin (area under the curve ×6) and paclitaxel (200 mg/m(2)) every 3 weeks (B + CP), or second-line bevacizumab plus erlotinib (150 mg/d; B + E). Six-month progression-free survival (PFS) was the primary endpoint. The trial could be stopped if there were more than three (B + CP) or more than two (B + E) intracranial hemorrhages.
  
  
  RESULTS
  In first-line B + CP cohort (n = 67), 6-month PFS rate was 56.5% with a median PFS of 6.7 months [95% confidence interval (CI), 5.7-7.1] and median overall survival (OS) of 16.0 months. Investigator-assessed overall response rate (ORR) was 62.7%: 61.2% in intracranial lesions and 64.2% in extracranial lesions. Because of low enrolment (n = 24), efficacy results for the second-line B + E cohort were exploratory only; 6-month PFS rate was 57.2%, median PFS was 6.3 months (95% CI, 3.0-8.4), median OS was 12.0 months, and ORR was 12.5%. Adverse events were comparable with previous trials of bevacizumab. One grade 1 intracranial hemorrhage occurred and resolved without sequelae.
  
  
  CONCLUSIONS
  The BRAIN study demonstrates encouraging efficacy and acceptable safety of bevacizumab with first-line paclitaxel and carboplatin in patients with NSCLC and asymptomatic, untreated brain metastases.
authors.affiliation: Gustave Roussy, Villejuif France and Paris Sud University, France. benjamin.besse@gustaveroussy.fr.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Besse
authors.affiliation: Hôpital d'Instruction des Armées du Val-de-Grâce, Paris, France.
authors.forename: Sylvestre
authors.initials: S
authors.lastname: Le Moulec
authors.affiliation: CHU Toulouse - Hôpital De Larrey, Toulouse, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Mazières
authors.affiliation: Institut De Cancérologie De l'Ouest, Site René Gauducheau, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Senellart
authors.affiliation: Aix-Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Barlesi
authors.affiliation: CHI Crétiel, Crétreil, France.
authors.forename: Christos
authors.initials: C
authors.lastname: Chouaid
authors.affiliation: CLCC Oscar Lambret, Lille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Dansin
authors.affiliation: Hôpital d'Instruction des Armées Sainte Anne, France.
authors.forename: Henri
authors.initials: H
authors.lastname: Bérard
authors.affiliation: L'Hôpital Nord Ouest, Villefranche Sur Saone, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Falchero
authors.affiliation: Centre François Baclesse, Caen, France.
authors.forename: Radj
authors.initials: R
authors.lastname: Gervais
authors.affiliation: CHU Morvan, Brest, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Robinet
authors.affiliation: Hôpital Tenon, APHP, Paris, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Ruppert
authors.affiliation: Centre Paul Strauss, Strasbourg, France.
authors.forename: Roland
authors.initials: R
authors.lastname: Schott
authors.affiliation: CHU Rennes, Hôpital Pontchaillou, Rennes, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Léna
authors.affiliation: Hôpital de Brabois, Vandoeuvre-lès-Nancy, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Clément-Duchêne
authors.affiliation: CHU Montpellier and ICM Val d'Aurelle, Montpellier, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Quantin
authors.affiliation: Centre Hospitalier de Lyon Sud, Lyon, France.
authors.forename: Pierre Jean
authors.initials: PJ
authors.lastname: Souquet
authors.affiliation: Hôpital Saint-Joseph, Paris, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Trédaniel
authors.affiliation: CHU De Grenoble, Hôpital A. Michalon, La Tronche, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Moro-Sibilot
authors.affiliation: Centre Leon Bérard, Lyon, France.
authors.forename: Maurice
authors.initials: M
authors.lastname: Pérol
authors.affiliation: Institut Paoli Calmettes, Marseille, France.
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Madroszyk
authors.affiliation: Gustave Roussy, Villejuif France and Paris Sud University, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D019233:Retreatment; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D000068258:Bevacizumab