title: Pazopanib as a second-line treatment for non-cytokine-treated metastatic renal cell carcinoma: a meta-analysis of the effect of treatment.
abstract: BACKGROUND
  The currently recommended treatment algorithm for patients with advanced renal cell carcinoma who fail the first-line targeted therapy does not normally include pazopanib as a second-line treatment option. It would therefore be of interest to determine the efficiency of pazopanib in this setting in terms of the partial response rate (PRR), disease control rate (DCR), and progression-free survival (PFS).
  
  
  METHODS
  Peer-reviewed clinical reports without language restriction, both full papers and conference abstracts, which assessed the second-line use of pazopanib following failure of first-line non-cytokine-targeted therapy, were included. After the literature retrieval, we conducted a Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-compliant systematic review of the literature and meta-analysis of the size of the effect of each outcome measure (PRR, DCR, and PFS). The effect size and 95 % confidence interval (CI) were calculated using fixed-effect or random-effects models based on the heterogeneity represented by I(2) of selected studies. Meta-analysis forest plots with a fixed-effect model showing the PRR and DCR were created.
  
  
  RESULTS
  Our results show that there are no available comparative studies on pazopanib second-line treatment. Only phase II trials or retrospective analysis reports were retrievable. Six studies (comprising 217 patients) were included in the qualitative and quantitative analysis. Pazopanib as a second-line treatment resulted in a PRR of 23 % (95 % CI, 17-31 %; I(2) = 52.6 %) and a DCR of 73 % (95 % CI, 65-80 %; I(2) = 0.00 %). The meta-analysis with fixed-effect model revealed that PFS was 6.5 months (95 % CI, 5.6-7.5 months; I(2) = 86.2 %).
  
  
  CONCLUSIONS
  In conclusion, the effectiveness and indication of pazopanib for use in the second-line setting has not yet been examined in-depth; however, this meta-analysis has shown that the treatment effects in terms of PRR, DCR, and PFS may be similar to other well-studied second-line targeted therapies. Rigorous comparative phase III trials testing this hypothesis are required.
authors.affiliation: Division of Medical Oncology, Cancer Center of Kuang Tien General Hospital, 117 Shatien Rd, Taichung, 43303, Taiwan. victorkok@asia.edu.tw.|Department of Biomedical Informatics, Asia University, Taichung, 41354, Taiwan. victorkok@asia.edu.tw.
authors.forename: Victor C
authors.initials: VC
authors.lastname: Kok
authors.affiliation: Division of Biostatistics, Institute of Public Health, School of Medicine, National Yang-Ming University, Taipei, 11221, Taiwan.
authors.forename: Jung-Tsung
authors.initials: JT
authors.lastname: Kuo
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary*; D018572:Disease-Free Survival; D006801:Humans; D007191:Indazoles; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D011743:Pyrimidines / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib
keywords: Meta-analysis; Pazopanib; Renal cell carcinoma; Second-line therapy; Targeted therapy