Summary by Dr. George Dranitsaris
Bevacizumab represents one of the first targeted agents that was been approved for the treatment of metastatic colorectal cancer (mCRC) in Canada. One of the reasons that the drug has generated so much interest is its high acquisition cost and the potential for serious, although relatively uncommon toxicities. One of the best methods to assess drug performance and safety is in the natural hospital setting. Therefore in this study, our objective was to evaluate safety and efficacy in the first series of patients that had received this agent in our province in the first two years of availability.
We identified 43 patients with mCRC who had received bevacizumab in combination with first line FOLFIRI chemotherapy. We adopted a longitudinal data collection format where the occurrences of adverse events following each cycle of treatment were assessed. Toxicity outcomes such as gastrointestinal (GI) perforations, bleeding, diarrhea, myelosuppression, proteinuria, and venous thromboembolic events (VTEs) were collected and graded using the NCI common toxicity criteria (V 3.0). Time to treatment failure (TTF) and overall survival (OS) were determined using the method of Kaplan–Meier.
• There were no GI perforations identified or cases of grade III/IV proteinuria.
• There were four bleeding events (9.3%), three requiring the permanent discontinuation of bevacizumab.
• There were six grade III/IV VTEs (14.0%), three of which required a hospital admission.
• There were five cases of grade III diarrhea (11.6%), one requiring a hospital admission and two needing rehydration.
• Median TTF and OS were 6.3 and 24.4 months, which are consistent with the findings from clinical trials.
Take home messages
• The findings suggested that this regimen is relatively well tolerated with the most serious adverse events being bleeding, diarrhea and VTE.
• The median TTF and OS estimated in our cohort study is comparable to that reported in the first line bevacizumab trials.
• The combination with FOLFIRI appears to be well tolerated and the side effects identified were consistent with those previously reported. However, clinicians need to monitor patients closely to avoid potentially serious events such as bleeding and VTEs. The development and validation of toxicity risk models to identify high risk patients would be helpful in this instance.