A meta-analysis of bevacizumab plus interferon alfa for previously untreated patients with metastatic clear-cell renal carcinoma (mRCC).

366 Background: mRCC was highly resistant to conventional chemotherapy. Both CALGB study and AVOREN study failed to detect statistic differences in overall survival (OS). To evaluate the effectiveness and adverse-effect of bevacizumab plus IFN-α for untreated mRCC, we performed a meta-analysis. Methods: We searched RCTs that compared bevacizumab plus IFN- alpha with other treatments. For trials without heterogeneity, meta-analysis was carried out by using review manager (Revman 4.2) with fixed or random-effects models. Hazard ratio (HR), relative risk (RR), and 95 percent confidence intervals (CI) were calculated. The primary outcome was overall survival. The secondary outcomes were PFS and the adverse effects. Subgroup analyses were performed by MSKCC risk factors. Results: Two RCTs (CALGB study and AVOREN study) were identified as eligible for inclusion in our meta-analysis. Overall survival: Meta- analysis including 1,381 patients showed a trend in favor of bevacizumab plus IFN-alpha with an HR of 0.89 (95% CI, 0.80-1.00, p=0.05). Meta-analysis of OS which adjusted on stratification factors showed extent improvement in favor of bevacizumab plus IFN-alpha (HR=0.86, 95% CI, 0.76-0.97, p=0.02). Progress-free survival: Meta-analyses showed statistic differences in favor of bevacizumab plus IFN-alpha in both unstratified PFS (HR=0.68, 95% CI, 0.61-0.77, p<0.00001) and stratified PFS (HR=0.67, 95% CI, 0.59-0.75, p<0.00001). Subgroup analysis: There were no statistic differences between bevacizumab plus IFN-alpha and IFN-alpha in MSKCC favorable risk group (HR=0.91, 95% CI, 0.70-1.17, p=0.45) and MSKCC poor risk group (HR=0.79, 95% CI, 0.55-1.14, p=0.21). For MSKCC intermediate risk group, there was statistic difference in favor of bevacizumab plus IFN-alpha (HR=0.85, 95% CI, 0.73-0.99, p=0.04). Adverse effects: There were statistic differences in favor ofIFN-alpha in anorexia, fatigue proteinuria, and bleeding, while no statistic difference in gastrointestinal perforation. Conclusions: Bevacizumab plus IFN-alpha prolonged both OS and PFS as first line therapy for mRCC, especially for MSKCC intermediate risk group. The toxicity was acceptable and well tolerated. No significant financial relationships to disclose.