title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Pegfilgrastim in Patients Receiving First-Line FOLFOX/Bevacizumab or FOLFIRI/Bevacizumab for Locally Advanced or Metastatic Colorectal Cancer: Final Results of the Pegfilgrastim and Anti-VEGF Evaluation Study (PAVES).
abstract: Pegfilgrastim's role in reducing the risk of febrile neutropenia (FN) in patients with colorectal cancer (CRC) receiving chemotherapy plus bevacizumab was not previously evaluated in a prospective study. The present phase III, double-blind trial evaluated the efficacy of pegfilgrastim versus placebo in reducing the incidence of grade 3/4 FN in patients with advanced CRC receiving bevacizumab combined with first-line chemotherapy (FOLFOX [leucovorin, 5-fluorouracil, oxaliplatin] or FOLFIRI [leucovorin, 5-fluorouracil, irinotecan]).
  
  
  
  Patients aged ≥ 18 years with locally advanced or metastatic CRC were randomized 1:1 to placebo or 6 mg of pegfilgrastim ∼24 hours after receiving chemotherapy plus bevacizumab every 14 days. The study treatment period included 4 cycles, but patients could continue treatment for ≤ 60 months. The primary endpoint was incidence of grade 3/4 FN in the first 4 cycles. The secondary endpoints included the objective response rate (ORR), overall survival, and progression-free survival, analyzed at the end of the long-term follow-up period.
  
  
  
  A total of 845 patients were randomized from November 2009 to January 2012 (422, pegfilgrastim; 423, placebo). Pegfilgrastim significantly reduced the incidence of grade 3/4 FN in the first 4 treatment cycles (pegfilgrastim, 2.4%; 95% confidence interval [CI], 1.1%-4.3%; placebo, 5.7%; 95% CI, 3.7%-8.3%; odds ratio [OR], 0.41; P = .014). No significant differences were observed between the 2 arms in ORR (OR, 1.15; P = .330), overall survival (hazard ratio, 0.94; P = .440), and progression-free survival (hazard ratio, 0.93; P = .300).
  
  
  
  Pegfilgrastim reduced the FN incidence in patients with advanced CRC receiving chemotherapy and bevacizumab. Administration of pegfilgrastim was tolerable and did not negatively affect the tumor response or survival in this patient population.
authors.affiliation: Department of Oncoradiology, Petz Aladár Teaching Hospital, Györ, Hungary. Electronic address: pinterbely@gmail.com.
authors.forename: Tamás
authors.initials: T
authors.lastname: Pinter
authors.affiliation: Clinical Development, Amgen Inc, Thousand Oaks, CA.
authors.forename: Zandra
authors.initials: Z
authors.lastname: Klippel
authors.affiliation: Department of Medical Oncology, Klaipeda University Hospital, Klaipeda, Lithuania.
authors.forename: Alvydas
authors.initials: A
authors.lastname: Cesas
authors.affiliation: Department of Medical Oncology, Fundeni Clinical Institute, Bucharest, Romania.
authors.forename: Adina
authors.initials: A
authors.lastname: Croitoru
authors.affiliation: Department of Oncology, AZ Delta Hospital, Roeselare, Belgium.
authors.forename: Jochen
authors.initials: J
authors.lastname: Decaestecker
authors.affiliation: Department of Oncology, The Western Hospital, Footscray, Victoria, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Gibbs
authors.affiliation: Uzhgorod Regional Oncology Dispensary, Uzhgorod National University, Uzhgorod, Ukraine.
authors.forename: Yevhen
authors.initials: Y
authors.lastname: Hotko
authors.affiliation: Department of Oncology and Radiotherapy, Medical University Gdansk, Gdansk, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
authors.affiliation: Clinic of Medical Oncology, Specialized Hospital for Active Treatment in Oncology Sofia, Sofia, Bulgaria.
authors.forename: Galina
authors.initials: G
authors.lastname: Kurteva
authors.affiliation: Department of Oncology, Institute of Oncology and Rehabilitation, Nová Ves pod Pleší, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Novotny
authors.affiliation: Department of Medical Oncology, Ireland Cooperative Oncology Research Group, Dublin, Ireland.
authors.forename: Seamus
authors.initials: S
authors.lastname: O'Reilly
authors.affiliation: Department of Clinical Oncology, National Cancer Institute, Bratislava, Slovakia.
authors.forename: Tomas
authors.initials: T
authors.lastname: Salek
authors.affiliation: Global Biostatistical Sciences, Amgen Inc, Thousand Oaks, CA.
authors.forename: Maureen
authors.initials: M
authors.lastname: Reiner
authors.affiliation: Clinical Development, Amgen Inc, Thousand Oaks, CA.
authors.forename: Phuong Khanh
authors.initials: PK
authors.lastname: Morrow
authors.affiliation: Clinical Development, Amgen Inc, Thousand Oaks, CA.
authors.forename: Mi Rim
authors.initials: MR
authors.lastname: Choi
authors.affiliation: Clinical Development, Amgen Inc, Thousand Oaks, CA.
authors.forename: Sadie
authors.initials: S
authors.lastname: Whittaker
authors.affiliation: Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health & Sciences University, Portland, OR.
authors.forename: Charles
authors.initials: C
authors.lastname: Blanke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab / Q000008:administration & dosage; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004311:Double-Blind Method; D064147:Febrile Neutropenia / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control*; D005260:Female; D000069585:Filgrastim / Q000008:administration & dosage*; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: D009944:Organoplatinum Compounds; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D000069585:Filgrastim; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: Chemotherapy; Febrile neutropenia; Objective response rate; Overall survival; Progression-free survival