Five trials were included in the review (n=3,841 patients). The sample size of included trials ranged from 462 to 736 patients.
Progression-free survival: Compared with chemotherapy alone, the addition of bevacizumab to chemotherapy was associated with a significant improvement in progression-free survival for the first-line treatment (HR 0.68, 95% CI 0.56 to 0.81; NNT=12; three RCTs). Significant heterogeneity was observed for this outcome (p=0.0001). There was no significant difference in progression-free survival between the two groups for the second line treatment.
Overall survival: No significant difference in overall survival was observed between the two groups for both first-line and second-line treatment.
Overall response rate: Compared with chemotherapy alone, the addition of bevacizumab to chemotherapy was associated with a significant improvement in the overall response rate for the first-line treatment (RR 1.46, 95% CI 1.21 to 1.77; NNT=8 to 9; three RCTs) and a marginally significant improvement in the overall response rate for the second-line treatment (RR 1.58, 95% CI 1.00 to 2.52; NNT=12; two RCTs). Significant heterogeneity was observed for both of the outcomes (first-line treatment p=0.008; second-line treatment p=0.09).
Toxicity: Compared with chemotherapy alone, the addition of bevacizumab to chemotherapy was significantly associated with an increased risk of hypertension (RR 5.15, 95% CI 1.60 to 16.6; NNH=22). Significant heterogeneity was observed for this outcome (p<0.0001). The other significant adverse events were proteinuria, neurotoxicity, febrile neutropenia and bleeding.
Meta-regression showed that more than three metastatic sites, prior anthracycline-exposure, no adjuvant chemotherapy and negative hormonal receptor status significantly affected progression-free survival of patients for first-line treatment.