title: Common arm comparative outcomes analysis of phase 3 trials of cisplatin + irinotecan versus cisplatin + etoposide in extensive stage small cell lung cancer: final patient-level results from Japan Clinical Oncology Group 9511 and Southwest Oncology Group 0124.
abstract: BACKGROUND
  Southwest Oncology Group 0124 was a large North American phase 3 trial that failed to confirm a survival benefit for cisplatin/irinotecan over cisplatin/etoposide in patients with extensive stage small cell lung cancer (SCLC). These results were contrary to Japan Clinical Oncology Group 9511, a phase 3 trial exclusively in Japanese patients. Because 0124 and 9511 used identical treatment regimens and similar eligibility criteria, patient-level data were pooled from both trials, and a common arm analysis was performed to explore potential reasons for the divergent results.
  
  
  METHODS
  Patients with documented extensive stage SCLC and adequate end-organ function were randomized to intravenously receive either cisplatin 60 mg/m(2) Day 1 + irinotecan 60 mg/m(2) Days 1, 8, and 15 every 4 weeks or cisplatin 80 mg/m(2) Day 1 + etoposide 100 mg/m(2) Days 1-3 every 3 weeks. Demographic and outcome data were compared among 805 patients enrolled in 9511 and 0124 receiving identical treatment using a logistic model adjusted for age, sex, and performance status (PS).
  
  
  RESULTS
  Of 671 patients in 0124, 651 eligible patients were included, as were all 154 patients from 9511. Significant differences in sex and PS distribution as well as toxicity were seen between trials. There were also significant differences in response rates (87% vs 60%, P<.001) and median overall survival (12.8 vs 9.8 months, P<.001) when the cisplatin/irinotecan arms from both trials were compared.
  
  
  CONCLUSIONS
  Significant differences in patient demographics, toxicity, and efficacy were identified in the 9511 and 0124 populations. These results, relevant in the current era of clinical trials globalization, warrant: 1) consideration of differential patient characteristics and outcomes among populations receiving identical therapy; 2) utilization of the common arm model in prospective trials; and 3) inclusion of pharmacogenomic correlates in cancer trials where ethnic/racial differences in drug disposition are expected.
authors.affiliation: University of California Davis Cancer Center, Sacramento, California 95817, USA. primo.lara@ucdmc.ucdavis.edu
authors.forename: Primo N
authors.initials: PN
authors.lastname: Lara
authors.forename: Kari
authors.initials: K
authors.lastname: Chansky
authors.forename: Taro
authors.initials: T
authors.lastname: Shibata
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Fukuda
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tamura
authors.forename: John
authors.initials: J
authors.lastname: Crowley
authors.forename: Mary W
authors.initials: MW
authors.lastname: Redman
authors.forename: Ronald
authors.initials: R
authors.lastname: Natale
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Saijo
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002945:Cisplatin / Q000008:administration & dosage*; D017326:Clinical Trials, Phase III as Topic; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D000077146:Irinotecan; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D005047:Etoposide; D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin