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

Clin Colorectal Cancer. 2017 Jun;16(2):e61-e72. doi: 10.1016/j.clcc.2016.08.006. Epub 2016 Aug 31.

Abstract

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.

Keywords: Chemotherapy; Elderly; First-line; Overall survival; Progression-free survival.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bevacizumab / administration & dosage
  • Capecitabine / administration & dosage
  • Colorectal Neoplasms / drug therapy*
  • Disease-Free Survival
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Male
  • Neoplasm Metastasis
  • Randomized Controlled Trials as Topic
  • Survival Rate

Substances

  • Bevacizumab
  • Capecitabine
  • Fluorouracil