title: Second-line treatments for the management of advanced renal cell carcinoma: systematic review and meta-analysis.
abstract: OBJECTIVE
  A systematic review/meta-analysis was conducted to assess the effectiveness and safety of second-line treatments for advanced renal cell carcinoma (RCC), which includes the vascular endothelial growth factor inhibitor axitinib.
  
  
  METHODS
  Database searches were conducted to identify randomised controlled trials (RCTs). Indirect comparisons using a fixed-effect Bayesian model were used to assess the relative effectiveness of treatments and reported as hazard ratio (HR) and 95% credible intervals (CrI).
  
  
  RESULTS
  Although 24 RCTs met eligibility criteria, only three studies were included in the fixed-effect Bayesian meta-analysis, due to differences in patient inclusion criteria/reported outcomes in the wider dataset. Robust meta-analysis was restricted to the subgroup pretreated with cytokines. In terms of progression-free survival (PFS), axitinib was superior compared with placebo (HR = 0.25, 95% CrI: 0.17 - 0.38), sorafenib (HR = 0.46, 95% CrI: 0.32 - 0.68) and pazopanib (HR = 0.47, 95% CrI: 0.26 - 0.85). An analysis including all patients, regardless of previous first-line treatment, reported similar results. There was no significant difference in PFS between sorafenib and pazopanib.
  
  
  CONCLUSIONS
  Results from the present study suggest that axitinib will be an important treatment option to extend PFS in the management of advanced RCC in the second-line setting. Ongoing research will define the optimal treatment algorithm leading to a patient-focused treatment strategy.
authors.affiliation: Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK.
authors.forename: James
authors.initials: J
authors.lastname: Larkin
authors.forename: Abby
authors.initials: A
authors.lastname: Paine
authors.forename: Indra
authors.initials: I
authors.lastname: Tumur
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Cappelleri
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Healey
authors.forename: Grace
authors.initials: G
authors.lastname: Foley
authors.forename: Stephen
authors.initials: S
authors.lastname: Mitchell
authors.forename: Michel
authors.initials: M
authors.lastname: Kroes
authors.forename: Connie
authors.initials: C
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077784:Axitinib; D001499:Bayes Theorem; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007191:Indazoles / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D000077157:Sorafenib; D013449:Sulfonamides / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007093:Imidazoles; D007191:Indazoles; D010671:Phenylurea Compounds; D011743:Pyrimidines; D013449:Sulfonamides; D009536:Niacinamide; C516667:pazopanib; D000077157:Sorafenib; D000077784:Axitinib