title: Randomized phase II study of first-line carboplatin-paclitaxel with or without bevacizumab in Japanese patients with advanced non-squamous non-small-cell lung cancer.
abstract: OBJECTIVE
  This multicenter, randomized, open-label, phase II study (JO19907) compared the efficacy and safety of first-line carboplatin-paclitaxel (CP) alone with bevacizumab-CP in Japanese patients with advanced non-squamous non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Chemonaïve patients with stage IIIB, IV or recurrent non-squamous NSCLC were eligible for participation. Patients were randomly assigned in a 2:1 ratio to receive bevacizumab-CP or CP alone. Chemotherapy was repeated for up to 6 cycles or until disease progression or unacceptable toxicity. Bevacizumab recipients who completed ≥3 cycles of chemotherapy could continue bevacizumab as monotherapy until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS).
  
  
  RESULTS
  After confirming the tolerability of bevacizumab-CP in a small number of patients, 180 patients were recruited, of whom 121 were assigned to bevacizumab-CP and 59 to CP alone. Hazard ratio (HR) for PFS was 0.61 with bevacizumab-CP versus CP alone (p=0.0090; median 6.9 versus 5.9 months). Objective response rate was significantly higher with bevacizumab-CP than with CP alone (60.7% versus 31.0%; p=0.0013). Median overall survival was >22 months in both treatment groups (HR 0.99; p=0.9526). No new safety signals were detected.
  
  
  CONCLUSIONS
  Study JO19907 met its primary endpoint, demonstrating that the addition of bevacizumab to first-line CP significantly improves PFS in Japanese patients with advanced non-squamous NSCLC. This prolonged PFS by bevacizumab did not translate into OS benefit with the extremely longer underlying survival compared to historical data. No new safety signals were identified in this population. (Japan Pharmaceutical Information Center [JAPIC] registration number: CTI-060338).
authors.affiliation: National Cancer Center Hospital East, Chiba, Japan. siniho@east.ncc.go.jp
authors.forename: Seiji
authors.initials: S
authors.lastname: Niho
authors.forename: Hideo
authors.initials: H
authors.lastname: Kunitoh
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nokihara
authors.forename: Takeshi
authors.initials: T
authors.lastname: Horai
authors.forename: Yukito
authors.initials: Y
authors.lastname: Ichinose
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Hida
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kawahara
authors.forename: Tetsu
authors.initials: T
authors.lastname: Shinkai
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Kaoru
authors.initials: K
authors.lastname: Matsui
authors.forename: Shunichi
authors.initials: S
authors.lastname: Negoro
authors.forename: Akira
authors.initials: A
authors.lastname: Yokoyama
authors.forename: Shinzoh
authors.initials: S
authors.lastname: Kudoh
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Mori
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakai
authors.forename: Koji
authors.initials: K
authors.lastname: Takeda
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yokota
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Saijo
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuoka
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D044466:Asian People; D000068258:Bevacizumab; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D016190:Carboplatin; D017239:Paclitaxel