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)

Autor: Sadie Whittaker, Zandra Klippel, Peter Gibbs, Adina Croitoru, Mi Rim Choi, Tamás Pintér, Jacek Jassem, Yevhen Hotko, Tomas Salek, Seamus O'Reilly, Jan Novotny, Jochen Decaestecker, G. Kurteva, Phuong Khanh Morrow, Charles D. Blanke, Alvydas Česas, Maureen Reiner
Rok vydání: 2017
Předmět:
Male
Vascular Endothelial Growth Factor A
0301 basic medicine
Oncology
Organoplatinum Compounds
Leucovorin
Polyethylene Glycols
0302 clinical medicine
FOLFOX
Antineoplastic Combined Chemotherapy Protocols
Prospective Studies
Neoplasm Metastasis
Aged
80 and over
Incidence
Gastroenterology
Middle Aged
Bevacizumab
Survival Rate
030220 oncology & carcinogenesis
FOLFIRI
Female
Fluorouracil
Colorectal Neoplasms
Pegfilgrastim
medicine.drug
Adult
medicine.medical_specialty
Filgrastim
Disease-Free Survival
Young Adult
03 medical and health sciences
Double-Blind Method
Internal medicine
medicine
Humans
Progression-free survival
Survival rate
Aged
Febrile Neutropenia
Proportional Hazards Models
business.industry
medicine.disease
Surgery
Irinotecan
030104 developmental biology
Camptothecin
business
Febrile neutropenia
Follow-Up Studies
Zdroj: Clinical Colorectal Cancer. 16:103-114.e3
ISSN: 1533-0028
Popis: Background 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 and Methods 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. Results 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). Conclusion 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.
Databáze: OpenAIRE
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