title: FOLFIRI plus bevacizumab as second-line therapy in patients with metastatic colorectal cancer after first-line bevacizumab plus oxaliplatin-based therapy: the randomized phase III EAGLE study.
abstract: BACKGROUND
  A targeted agent combined with chemotherapy is the standard treatment in patients with metastatic colorectal cancer (mCRC). The present phase III study was conducted to compare two doses of bevacizumab combined with irinotecan, 5-fluorouracil/leucovorin (FOLFIRI) in the second-line setting after first-line therapy with bevacizumab plus oxaliplatin-based therapy.
  
  
  METHODS
  Patients were randomly assigned to receive FOLFIRI plus bevacizumab 5 or 10 mg/kg in 2-week cycles until disease progression. The primary end point was progression-free survival (PFS), and secondary end points included overall survival (OS), time to treatment failure (TTF), and safety.
  
  
  RESULTS
  Three hundred and eighty-seven patients were randomized between September 2009 and January 2012 from 100 institutions in Japan. Baseline patient characteristics were well balanced between the two groups. Efficacy was evaluated in 369 patients (5 mg/kg, n = 181 and 10 mg/kg, n = 188). Safety was evaluated in 365 patients (5 mg/kg, n = 180 and 10 mg/kg, n = 185). The median PFS was 6.1 versus 6.4 months (hazard ratio, 0.95; 95% confidence interval [CI] 0.75-1.21; P = 0.676), and median TTF was 5.2 versus 5.2 months (hazard ratio, 1.01; 95% CI 0.81-1.25; P = 0.967), respectively, for the bevacizumab 5 and 10 mg/kg groups. Follow-up of OS is currently ongoing. Adverse events, including hypertension and hemorrhage, occurred at similar rates in both groups.
  
  
  CONCLUSIONS
  Bevacizumab 10 mg/kg plus FOLFIRI as the second-line treatment did not prolong PFS compared with bevacizumab 5 mg/kg plus FOLFIRI in patients with mCRC. If bevacizumab is continued after first-line therapy in mCRC, a dose of 5 mg/kg is appropriate for use as second-line treatment.
  
  
  BACKGROUND
  UMIN000002557.
authors.affiliation: Department of Surgery, Kansai Medical University Hirakata Hospital, Hirakata iwamoto@hirakata.kmu.ac.jp.
authors.forename: S
authors.initials: S
authors.lastname: Iwamoto
authors.affiliation: Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu.
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Gastroenterological Surgery, Osaka General Medical Center, Osaka.
authors.forename: H
authors.initials: H
authors.lastname: Tamagawa
authors.affiliation: Aizawa Comprehensive Cancer Center, Aizawa Hospital, Matsumoto.
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Surgery, Fukuiken Saiseikai Hospital, Fukui.
authors.forename: Y
authors.initials: Y
authors.lastname: Munemoto
authors.affiliation: Department of Surgery, Kansai Rosai Hospital, Amagasaki.
authors.forename: T
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Surgery, Osaka University, Suita.
authors.forename: T
authors.initials: T
authors.lastname: Hata
authors.affiliation: Department of Gastroenterology, Chiba Cancer Center, Chiba.
authors.forename: T
authors.initials: T
authors.lastname: Denda
authors.affiliation: Department of Radiology, Kobe Medical Center, Kobe.
authors.forename: Y
authors.initials: Y
authors.lastname: Morita
authors.affiliation: Department of Integrated Medicine, Kagawa University, Kita.
authors.forename: M
authors.initials: M
authors.lastname: Inukai
authors.affiliation: Department of Surgery, Gifu Prefectural General Medical Center, Gifu.
authors.forename: K
authors.initials: K
authors.lastname: Kunieda
authors.affiliation: Department of Surgery, Kitakyushu General Hospital, Kitakyusyu.
authors.forename: N
authors.initials: N
authors.lastname: Nagata
authors.affiliation: Second Department of Surgery, Hamamatsu University School of Medicine, Shizuoka.
authors.forename: K
authors.initials: K
authors.lastname: Kurachi
authors.affiliation: Department of Medical Oncology, Nagoya Memorial Hospital, Nagoya.
authors.forename: K
authors.initials: K
authors.lastname: Ina
authors.affiliation: Department of Surgery, Toho University Medical Center Sakura Hospital, Sakura.
authors.forename: M
authors.initials: M
authors.lastname: Ooshiro
authors.affiliation: Department of Chemotherapy, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo.
authors.forename: T
authors.initials: T
authors.lastname: Shimoyama
authors.affiliation: Department of Gastroenterological Surgery, Kumamoto University, Kumamoto.
authors.forename: H
authors.initials: H
authors.lastname: Baba
authors.affiliation: Department of Biostatistics, School of Public Health, Graduate School of Medicine and Interfaculty Initiative in Information Studies, The University of Tokyo, Tokyo.
authors.forename: K
authors.initials: K
authors.lastname: Oba
authors.affiliation: Tokai Central Hospital, Kagamihara.
authors.forename: J
authors.initials: J
authors.lastname: Sakamoto
authors.affiliation: Cancer Center, Aichi Medical University, Nagakute, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Mishima
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011379:Prognosis; D016879:Salvage Therapy; D015996:Survival Rate
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: bevacizumab; chemotherapy; dose; metastatic colorectal cancer; randomized controlled trial; second-line therapy