Therapeutic effects and associated adverse events of first-line treatments of advanced renal cell carcinoma (RCC): a meta-analysis

Purpose: To compare the therapeutic effects and adverse events (AE) of current first-line treatments of advanced RCC, including sorafenib, sunitinib, temsirolimus, and the combination of bevacizumab and IFN-α. Methods: We performed a meta-analysis of randomized controlled trials of the effectiveness of the five treatments among patients with advanced RCC. The data of progressive disease, objective response rate (ORR), disease control rate (DCR), grade 3/4 AE, progression-free survival (PFS), and overall survival (OS) were extracted to assess therapeutic effects, toxicity, and prognosis, respectively. Results: Two studies that assessed the combination of bevacizumab with IFN α (n = 1381), one sunitinib (n = 750), one sorafenib (n = 189) and one temsirolimus (n = 416) were included. Sorafenib, sunitinib, temsirolimus (R = 0.35, 95 % confidence interval [CI] 0.26–0.48, P < 0.01), and the combination of bevacizumab with IFN (R = 0.64, 95 % CI 0.42–0.99, P = 0.04) were more effective in controlling tumor progression than IFN. Sorafenib, sunitinib, and temsirolimus do not own advantage in ORR compared with IFN (R = 2.06, 95 % CI 0.53–7.95, P = 0.30), but combination of bevacizumab with IFN showed better results in ORR than IFN (R = 2.56, 95 % CI 1.91–3.42, P < 0.01). Sorafenib, sunitinib, temsirolimus (R = 2.90, 95 % CI 2.23–3.78, P < 0.01), and combination of bevacizumab with IFN (R = 2.14, 95 % CI 1.65–2.78, P < 0.01) were more effective than IFN in DCR. Sorafenib, sunitinib, and temsirolimus had similar rate of grade 3/4 AE as IFN (R = 1.21, 95 % CI 0.96–1.51, P = 0.10). Combined use of bevacizumab and IFN is associated with higher frequency of the AE (R = 2.09, 95 % CI 1.66–2.63, P < 0.01). Sorafenib and sunitinib had similar median PFS (R = 0.67, 95 % CI 0.42–1.08, P = 0.10); temsirolimus had longer median OS (R = 0.82, 95 % CI 0.67–1.00, P = 0.049) as IFN. Combined use of bevacizumab and IFN had longer median PFS (R = 0.68, 95 % CI 0.60–0.76, P < 0.01) and OS (R = 0.86, 95 % CI 0.76–0.97, P = 0.01) than IFN. Conclusion: Sorafenib, sunitinib, temsirolimus, and the combination of bevacizumab with IFN are more effective in stabilizing disease. Combined use of bevacizumab and IFN is better than sorafenib, sunitinib, and temsirolimus in ORR, PFS, and OS, but associated with higher level of AE.