The impact of Bevacizumab (Avastin) on survival in metastatic solid tumors--a meta-analysis and systematic review.
OBJECTIVE
To evaluate the effect of Bevacizumab in combination with chemotherapy on overall survival of patients with metastatic solid tumors.


METHODS
A systematic literature search to identify randomized trials comparing chemotherapy with and without Bevacizumab in metastatic cancer. The primary end point was overall survival (OS) and the secondary end points were progression free survival (PFS) and toxicity. A meta-analysis was performed for each tumor type and for the combination of all tumors.


RESULTS
24 randomized trials with 8 different types of malignancies were included in this meta-analysis. Patients treated with Bevacizumab had an OS benefit, hazard ratio (HR) 0.89 (95% CI 0.84-0.93, P<0.00001 I(2)-4%). The combined analysis showed a PFS benefit with a HR 0.71 (95% CI 0.68-0.74, P<0.00001, I(2)-54%). The toxicity analysis showed a statistically significant increase in fatal adverse events (FAEs) in the Bevacizumab treatment arm, risk ratio (RR) 1.47 (95% CI 1.1-1.98). A separate analysis of the lung cancer trials showed an increased risk of fatal pulmonary hemorrhage with a RR of 5.65 (95% CI 1.26-25.26). The risk of G3-4 adverse events was increased: RR 1.2 (95% CI 1.15-1.24).


CONCLUSIONS
in this combined analysis Bevacizumab improved OS (with little heterogeneity) and PFS. These results should be considered in the light of lack of markers predictive of response and the increased severe and fatal toxicity seen with Bevacizumab treatment.
Institute of Oncology, Rabin Medical Center, Beilinson Campus, Petach Tiqwa, Israel. limor.amit@gmail.com
Limor
L
Amit
Irit
I
Ben-Aharon
Liat
L
Vidal
Leonard
L
Leibovici
Salomon
S
Stemmer
D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000068258:Bevacizumab; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016019:Survival Analysis
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab