Six randomised controlled trials were included in the review (3,060 patients, range 104 to 1,400). Five trials used adequate randomisation. Four trials reported blinding. Four trials used intention-to-treat analysis.
Meta-analysis showed that there was an advantage of using bevacizumab for progression-free survival (HR 0.72, 95% CI 0.66 to 0.78; Ι²=69%) and overall survival (HR 0.84, 95% CI 0.77 to 0.91; Ι²=60%). However, there was significant heterogeneity for both outcomes.
Studies where bevacizumab was administered with irinotecan-based chemotherapy, oxaliplatin-based chemotherapy and 5-fluorouracil monotherapy regimens were pooled separately. There was a statistically significant benefit with bevacizumab for overall survival as part of a irinotecan-based regimen only, and this was influenced by a single study. There was a statistically significant benefit with bevacizumab for progression-free survival in each of the subgroups. When studies were subgrouped by mode of administration of 5-fluorouracil (bolus, infusion, capecitabine-based), there was a benefit with bevacizumab for the bolus 5-fluorouracil and capecitabine-based regimens.
Overall response rate showed no significant favourable results of bevacizumab. For treatment-related toxicity, bevacizumab was associated with increased rates of hypertension, proteinuria, bleeding, thromboembolic events and treatment interruptions but no difference in haematologic toxicity and gastrointestinal perforation.