Impact of cardiovascular comorbidities on the effectiveness of bevacizumab in elderly patients with metastatic colorectal cancer (IRAZU)

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Effectiveness study (incl. comparative)

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (L01XC07) bevacizumab

  bevacizumab
• Medical condition to be studied:
  Colorectal cancer metastatic

Population studied

• Age groups:
  • Adult and elderly population (≥18 years)

    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Estimated number of subjects:
  16000

Study design details

• Main study objective:
  The main objective of this study is to evaluate the impact of the presence of cardiovascular comorbidities at baseline on 36-month overall survival in elderly mCRC patients treated with bevacizumab.
• Outcomes:
  Occurrence of death from any cause at 36 months. Occurrence of death from any cause at 12 and 24 months. Occurrence of each of the following serious cardiovascular event: heart failure, malignant hypertension and thromboembolic events (including myocardial infarction, venous and arterial thrombosis, stroke and pulmonary embolism) during the follow-up. Occurrence of a composite endpoint of serious cardiovascular events during the follow-up.
• Data analysis plan:
  The probability of death will be evaluated at 12, 24 and 36 months using Kaplan-Meier analyses and will be compared across groups using the log rank test. The impact of cardiovascular comorbidities on 36-month risk of death and on the occurrence of serious cardiovascular events will be evaluated using time-dependent multivariable proportional hazards Cox regression models (for death) and Fine and Gray models taking into account death as a competing risk (for occurrence of cardiovascular events only). A sensitivity “on-treatment” analysis will be carried-out. The safety will be assessed between the first dispensing of bevacizumab and the date of the considered cardiovascular events (separately or combined) or the last dispensing of first-line bevacizumab during the follow-up whichever came first. All analyses will be stratified according to age at mCRC diagnosis: <75 versus ≥75 years old.