title: A phase 2 study of bevacizumab in combination with carboplatin and paclitaxel in patients with non-squamous non-small-cell lung cancer harboring mutations of epidermal growth factor receptor (EGFR) after failing first-line EGFR-tyrosine kinase inhibitors (HANSHIN Oncology Group 0109).
abstract: OBJECTIVE
  We have conducted a phase 2 study to evaluate the efficacy and safety of carboplatin, paclitaxel, and bevacizumab in patients with non-squamous non-small-cell lung cancer (NSCLC) who are epidermal growth factor receptor (EGFR) mutation positive and for whom EGFR-tyrosine kinase inhibitor (TKI) 1st-line has failed.
  
  
  METHODS
  Patients with stage IIIB or IV non-squamous NSCLC harbored activating EGFR mutations that has failed 1st-line EGFR-TKI and an Eastern Cooperative Oncology Group performance status of 0 or 1 were included in this study. Patients received carboplatin at an area under the concentration-time curve 5 or 6, paclitaxel 200mg/m(2), and bevacizumab 15mg/kg on D1. The combination therapy was repeated every 21 days for up to three to six cycles. Bevacizumab was continued until disease progression or unacceptable toxicity for patients without disease progression (PD). The primary endpoint was objective response rate (ORR).
  
  
  RESULTS
  Thirty-one patients were enrolled between March 2010 and January 2013, with 30 patients being eligible. ORR was 37% (90% CI; 24-52%) and disease control rate, 83% (95% CI; 66-92%). The median progression free survival (PFS) was 6.6 months (95% CI; 4.8-12.0 months) and median overall survival, 18.2 months (95% CI; 12.0-23.4 months). The most common grade ≥3 hematologic toxicity was neutropenia (93%), and non-hematologic toxicity, febrile neutropenia (20%). There were no clinically relevant grade ≥3 bleeding events and no treatment-related deaths.
  
  
  CONCLUSIONS
  The combination therapy of carboplatin, paclitaxel and bevacizumab did not achieve the initial treatment goal.
authors.affiliation: Department of Thoracic Oncology, Hyogo Cancer Center, Akashi, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hattori
authors.affiliation: Department of Thoracic Oncology, Hyogo Cancer Center, Akashi, Japan. Electronic address: satouchi@hp.pref.hyogo.jp.
authors.forename: Miyako
authors.initials: M
authors.lastname: Satouchi
authors.affiliation: Department of Thoracic Oncology, Hyogo Cancer Center, Akashi, Japan.
authors.forename: Temiko
authors.initials: T
authors.lastname: Shimada
authors.affiliation: Department of Thoracic Oncology, Hyogo Cancer Center, Akashi, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Urata
authors.affiliation: Department of Thoracic Oncology, National Hospital Organization Toneyama National Hospital, Toyonaka, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yoneda
authors.affiliation: Department of Thoracic Oncology, National Hospital Organization Toneyama National Hospital, Toyonaka, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Respiratory Medicine, Kyoto Katsura Hospital, Kyoto, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishimura
authors.affiliation: Department of Respiratory Medicine, Kyoto Katsura Hospital, Kyoto, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sunadome
authors.affiliation: Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kumagai
authors.affiliation: Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Imamura
authors.affiliation: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Fujita
authors.affiliation: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Kaji
authors.affiliation: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, Japan.
authors.forename: Akito
authors.initials: A
authors.lastname: Hata
authors.affiliation: Department of Respiratory Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Tachihara
authors.affiliation: Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.affiliation: Department of Medical Oncology, Hyogo Cancer Center, Akashi, Japan.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Negoro
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D012008:Recurrence; D019233:Retreatment; D012307:Risk Factors; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000068258:Bevacizumab; D016190:Carboplatin; C512478:EGFR protein, human; D066246:ErbB Receptors; D017239:Paclitaxel
keywords: Bevacizumab; Carboplatin; Epidermal growth factor receptor mutation; Non-small-cell lung cancer; Paclitaxel; Second-line