Efficacy and Safety of Bevacizumab Combined With Fluoropyrimidine Monotherapy for Unfit or Older Patients With Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis

Carmine Pinto, Lorenzo Antonuzzo, Luca Porcu, Giuseppe Aprile, Evaristo Maiello, Gianluca Masi, Fausto Petrelli, Mario Scartozzi, Valter Torri, Sandro Barni

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Background: Whether bevacizumab represents a feasible option for the first-line treatment of unfit and elderly patients with metastatic colorectal cancer (mCRC) remains controversial. The present systematic review and meta-analysis evaluated the efficacy and safety data of bevacizumab combined with first-line fluoropyrimidine monochemotherapy for these complex patients. Patients and Methods: A systematic search of the published data was conducted through May 31, 2016. The random-effects model was used to combine the effect estimates and the I2 index to quantify the between-study heterogeneity unexplained by sampling error. Results: We included 3 randomized controlled trials, 4 single-arm phase II trials, and 1 prospective cohort study in the present meta-analysis (n = 782). The monochemotherapy administered was capecitabine in 531 patients (67.9%) and 5-fluorouracil in 251 (32.1%); 500 (63.9%) also received bevacizumab. The median age was 75 years, 441 patients (56.4%) were men, and the Eastern Cooperative Oncology Group performance status was 0 to 1 in 684 patients (87.7%). The combination with bevacizumab produced advantages in terms of both progression-free survival (hazard ratio, 0.52; 95% confidence interval, 0.43-0.64; P < .00001; I2 = 0%) and overall survival (HR, 0.79; 95% CI, 0.64-0.98; P = .03; I2 = 0%). The pooled effect estimates of the randomized controlled trials have been previously reported. As expected, all-grade hypertension (27% vs. 4.9%), bleeding (24% vs. 6.4%), thromboembolic events (10% vs. 5%), and proteinuria (25.6% vs. 8.2%) were more frequent in the bevacizumab combination group. Conclusion: Adding bevacizumab to first-line fluoropyrimidine monochemotherapy significantly improved progression-free and overall survival in unfit and elderly patients with mCRC, with a manageable safety profile and no unexpected toxicities.

Original languageEnglish
JournalClinical Colorectal Cancer
Publication statusAccepted/In press - Apr 27 2016



  • Chemotherapy
  • Elderly
  • First-line
  • Overall survival
  • Progression-free survival

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology

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