title: Sex differences in outcome with bevacizumab therapy: analysis of patients with advanced-stage non-small cell lung cancer treated with or without bevacizumab in combination with paclitaxel and carboplatin in the Eastern Cooperative Oncology Group Trial 4599.
abstract: BACKGROUND
  E4599 compared carboplatin and paclitaxel with (PCB) or without (PC) bevacizumab in patients with advanced-stage non-small cell lung cancer. Bevacizumab improved overall survival. However, an unplanned subset analysis did not show a survival benefit for females treated with bevacizumab.
  
  
  METHODS
  Known prognostic factors and toxicities were compared by sex. Proportional hazards models of survival with multiple factor combinations were used to adjust for treatment effect.
  
  
  RESULTS
  The analysis includes 850 patients. The median survival was 8.7 months (PC) versus 11.7 months (PCB) for males (p = 0.001) and 13.1 months (PC) versus 13.3 months (PCB) for females (p = 0.87). Progression-free survival and response rate on the PCB arm were 6.3 months and 29% for males and 6.2 months and 41% for females (p > 0.05). Progression-free survival and response rate on the PC arm were 4.3 months and 16% for males and 5.3 months and 14% for females (p > 0.05). No significant demographic differences were seen between the two arms for males, whereas fewer females on the PCB arm had liver metastasis (PCB 11.7% versus PC 23.2%, p = 0.003). Adverse events with a sex difference on the PCB arm included severe hypertension (males: 4.2%, females: 9.9%, p = 0.02), constipation (males: 1.4%, females: 4.7%, p = 0.05), and abdominal pain (males: 0.9%, females: 5.2%, p = 0.01). In the proportional hazards model adjusting for the other factors, the test for a sex by treatment interaction was not significant (p = 0.09).
  
  
  CONCLUSIONS
  Multiple factors may contribute to the apparent sex-specific differences in efficacy of bevacizumab noted in this study.
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231-1000, USA. brahmju@jhmi.edu
authors.forename: Julie R
authors.initials: JR
authors.lastname: Brahmer
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Dahlberg
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Gray
authors.forename: Joan H
authors.initials: JH
authors.lastname: Schiller
authors.forename: Michael C
authors.initials: MC
authors.lastname: Perry
authors.forename: Alan
authors.initials: A
authors.lastname: Sandler
authors.forename: David H
authors.initials: DH
authors.lastname: Johnson
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000188:drug therapy* / Q000473:pathology; D000368:Aged; 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* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D008297:Male; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D012189:Retrospective Studies; D012737:Sex Factors; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D016190:Carboplatin; D017239:Paclitaxel