title: Treatment outcomes by tumor histology in Eastern Cooperative Group Study E4599 of bevacizumab with paclitaxel/carboplatin for advanced non-small cell lung cancer.
abstract: BACKGROUND
  The combination of paclitaxel/carboplatin (PC) and bevacizumab (B) was previously shown to extend overall survival (OS) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC). An analysis of survival and safety outcomes based on histology is presented here.
  
  
  METHODS
  Patients with cytologically or histologically confirmed metastatic NSCLC were treated with PC + B (PCB) or PC. Median OS for all patients was determined using Kaplan-Meier methodology. Hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained using an unstratified Cox proportional hazards model. Histology-by-treatment interaction was tested with an unstratified multivariate Cox regression model.
  
  
  RESULTS
  A total of 444 patients were randomized to PC, and 434 patients were randomized to PCB (the intent-to-treat population). Median OS times were 10.3 and 12.3 months for PC and PCB, respectively, with an HR for PCB of 0.80 (95% CI: 0.69-0.93). A total of 68.8% of patients had adenocarcinoma histology; 18.9% had "not otherwise specified"; 5.5% had large cell undifferentiated; 2.6% had bronchoalveolar carcinoma; and 3.9% "other." For adenocarcinoma, median OS was 10.3 months for PC treatment (n = 302) and 14.2 months for PCB (n = 300), HR 0.69 (95%CI: 0.58-0.83). Sample sizes for other specific histologic subtypes were too small for meaningful comparisons. Safety profiles among histologies were consistent with the overall safety profile, and there were no unexpected adverse event trends.
  
  
  CONCLUSIONS
  Addition of B to PC is associated with increased survival in previously untreated patients with nonsquamous NSCLC. Adenocarcinoma was associated with an increased survival benefit of PCB treatment. Data for other histologies are inconclusive, primarily because of small patient sample sizes and large CIs.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, USA. sandlera@ohsu.edu
authors.forename: Alan
authors.initials: A
authors.lastname: Sandler
authors.forename: Jing
authors.initials: J
authors.lastname: Yi
authors.forename: Suzanne
authors.initials: S
authors.lastname: Dahlberg
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Kolb
authors.forename: Lisa
authors.initials: L
authors.lastname: Wang
authors.forename: Julie
authors.initials: J
authors.lastname: Hambleton
authors.forename: Joan
authors.initials: J
authors.lastname: Schiller
authors.forename: David H
authors.initials: DH
authors.lastname: Johnson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D016190:Carboplatin; D017239:Paclitaxel