Addition of bevacizumab to fluorouracil-based first-line treatment of metastatic colorectal cancer: pooled analysis of cohorts of older patients from two randomized clinical trials

J Clin Oncol. 2009 Jan 10;27(2):199-205. doi: 10.1200/JCO.2008.17.7931. Epub 2008 Dec 8.

Abstract

Purpose: Colorectal cancer (CRC) occurs predominantly in older persons. To provide more statistical power to assess risk/benefit in older patients, we examined the clinical benefit of bevacizumab (BV) plus fluorouracil-based chemotherapy in first-line metastatic CRC (mCRC) treatment in patients aged > or = 65 years, using data pooled from two placebo-controlled studies.

Patients and methods: Pooled efficacy data for 439 patients > or = 65 years old randomized to BV plus chemotherapy (n = 218) or placebo plus chemotherapy (n = 221) in study 1 and study 2 were retrospectively analyzed on an intent-to-treat basis for overall survival (OS), progression-free survival (PFS), and objective response. Safety analysis was based on reports of targeted adverse events in treated patients.

Results: Median OS with BV plus chemotherapy was 19.3 v 14.3 months with placebo plus chemotherapy (hazard ratio [HR] = 0.70; 95% CI, 0.55 to 0.90; P = .006). Patients treated with BV plus chemotherapy had a median PFS of 9.2 v 6.2 months for placebo plus chemotherapy patients (HR = 0.52; 95% CI, 0.40 to 0.67; P < .0001). The objective response rate was 34.4% with BV plus chemotherapy versus 29.0% with placebo plus chemotherapy (difference not statistically significant). Rates of BV-associated adverse events in the pooled BV plus chemotherapy group were consistent with those reported in the overall populations for the two studies.

Conclusion: Analysis of pooled patient cohorts age >/= 65 years from two similar trials in mCRC indicates that adding bevacizumab to fluorouracil-based chemotherapy improved OS and PFS, similar to the benefits in younger patients. Also, the risks of treatment do not seem to exceed those in younger patients with mCRC.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Cohort Studies
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Humans
  • Infusions, Intravenous
  • Irinotecan
  • Leucovorin / administration & dosage
  • Male
  • Placebos
  • Retrospective Studies
  • Survival Rate

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Placebos
  • Bevacizumab
  • Irinotecan
  • Leucovorin
  • Fluorouracil
  • Camptothecin