Background: there are six new target therapeutic drugs approved for the treatment of metastatic renal cell carcinoma (mRCC) since 2006. At present, no direct head to head trial to compare their efficacy is available.
Methods: A systematic literature search of the MEDLINE, EMBASE, CANCERLIT and CENTRAL databases was performed. All randomized clinical trials of sorafenib, sunitinib, everolimus and pazopanib used to treat mRCC were included. The study selection, data extraction, and quality assessment were performed independently by two reviewers, with all disagreements resolved by consensus. The main outcome was benefit (defined as an improvement in progression median disease-free survival or overall survival). We did the network meta-analysis using mixed-effects logistic regression to perform an indirect comparison of the treatment effects between target therapeutic drugs. The quality appraisal was analyzed using the Jadad scale.
Results: Compared with placebo or interferon-α, target therapeutics may improve survival benefit (Hazard ratio (HR): 0.51, 95% CI 0.05 to 0.98). The proportion of patients who discontinued the study drug due to adverse events was similar between sorafenib and pazopanib; but everolimus was higher than sunitinib (10% in everolimus and 6% in the sunitinib). Sorafenib is likely less effective than other target therapeutics, although this difference was statistically significant for the comparison with sunitinib (HR: 0.47, 95% CI 0.316 to 0.713) and everolimus (HR: 0.159 95% CI 0.091 to 0.276). However, the effectiveness of sorafenib was not statistically different from pazopanib by using placebo as a comparator (HR: 0.957, 95% CI: 0.657 to 1.393). The results of quality assessment showed that 60% of studies were scored 5 and 40% were scored 3.
Conclusions: Our findings suggest that most of the targeted therapeutic drugs included in this study have reportedly favorable PFS or overall survival for patients with mRCC compared to IFN-α or placebo. Given the limitations of indirect comparisons, sorafenib is likely less effective than sunitinib and everolimus, but have similar effectiveness to pazopanib. Sunitinib was safer than everolimus, sorafenib and pazopanib. More RCTs are required to confirm these findings and investigate the clinical effectiveness of targeted therapeutics in the treatment of mRCC.