Sequential Therapy After The Failure Of Anti-angiogenesis Therapy In Advanced Renal Cell Carcinoma: A Meta Analysis

Renal cell carcinoma is the most common form of kidney malignant tumor,accounting for 3% of the adult malignancies. About third of patients present with metastatic disease at diagnosis, and 20%~40% of patients replase after operation.Advanced renal cell carcinoma is high invasive, and is not sensitive to the traditional radiotherapy and chemotherapy, cytokine therapy benefit is also limited. at present,the molecular targeted therapy has become the standard treatment, and anti-angiogenesis therapy is preferred the vast majority of patients. Although VEGF/VEGFR-targeted drugs significantly increased the patient’s disease control rates, prolong the survival time, but usually in 6 to 11 months disease progress. If drug resistance phenomenon occurring, sequencing another kind of tyrosine kinase inhibitor(TKI) or switch to mammalian target of rapamycin(m TOR) inhibitors, there is still controversy.Objective:To assess the efficacy and safety of m TOR inhibitors and TKIs in advanced renal cell carcinoma after the failure of anti-angiogenesis therapy.Materials and Methods:Electronic databases were searched for RCTs comparing m TOR inhibitors and TKIs in advanced renal cell carcinoma after the failure of anti-angiogenesis therapy,from 2004 to 2016. The relevant data of disease control rate(DCR), objective response rate(ORR), 1 year progression-free survival rate, progression free survival(PFS),overall survival(OS), and adverse events were collected. We used Revman 5.3software to perform the Meta analysis.Results:The present analysis contain three randomized controlled trials, encompassing1272 cases.Results showed that after the failure of anti-angiogenesis therapy, m TORinhibitor and TKI had no statistical differences in DCR(OR= 0.83, 95% CI [0.65,1.07], P = 0.16), ORR(OR=0.34, 95% CI [0.09, 1.27], P = 0.11), 1 year progression-free survival rate(OR= 0.66, 95% CI [0.42, 1.05], P = 0.08), PFS(HR=1.37, 95%CI [0.76, 2.47], P = 0.30), and incidence of Ⅲ/Ⅳ adverse events(OR=0.64, 95%CI [0.36, 1.12], P = 0.12). Compared with m TOR inhibitor, sequential application of TKI can get longer overall survival(HR = 1.39, 95% CI [1.18, 1.63], P< 0.01); In terms of safety, Ⅲ/Ⅳ anemia(OR= 3.45, P<0.01), hyperlipidemia(OR=2.77, P=0.02), high blood sugar(OR= 9.38, P<0.01) in m TOR inhibitors were significantly higher than TKI; While the TKI sequential therapy were more likely to happen Ⅲ / Ⅳ anorexia(OR=0.35, P=0.02), diarrhea(OR= 0.23, P<0.01),albuminuria(OR= 0.10, P< 0.01), and the differences were statistically significant.Conclusions:1. Compared with the m TOR inhibitor, sequential application of TKI can significantly prolong the overall survival in advanced renal cell carcinoma with the failure of anti-angiogenesis therapy.2. TKI and m TOR inhibitor are not statistically different in terms of ORR, DCR,1 year progression-free survival rate and PFS.3. In terms of safety, m TOR inhibitors have a higher incidence of anemia,hyperlipidemia and hyperglycemia; TKIs are prone to anorexia, diarrhea, and proteinuria. There is no statistical difference in the incidence of Ⅲ / Ⅳ adverse events.