title: Comparative effectiveness of approved first-line anti-angiogenic and molecularly targeted therapeutic agents in the treatment of good and intermediate risk metastatic clear cell renal cell carcinoma.
abstract: BACKGROUND
  Based on improved clinical outcomes in randomized controlled clinical trials (RCTs) the FDA and EMA have approved bevacizumab with interferon, sunitinib, and pazopanib in the first-line treatment of low to intermediate risk metastatic clear cell renal cell carcinoma (mRCC). However, there is little comparative data to help in choosing the most effective drug among these agents.
  
  
  METHODS
  We performed an indirect comparative effectiveness analysis of the pivotal RCTs of bevacizumab with interferon, sunitinib, or pazopanib compared to one another or interferon alone in first-line treatment of metastatic or advanced RCC. Endpoints of interest were overall survival (OS), progression free survival (PFS), and response rate (RR). Adverse events were also examined.
  
  
  RESULTS
  The meta-estimate of the hazard ratio (95% confidence interval) for OS for bevacizumab with interferon vs. interferon alone was 0.86 (0.76-0.97), for sunitinib vs. interferon alone was 0.82 (0.67-1.00), for pazopanib vs. interferon alone was 0.74 (0.57-0.97), for sunitinib vs. bevacizumab with interferon was 0.95 (0.75-1.20), for pazopanib vs. bevacizumab with interferon was 0.86 (0.64-1.16), and for pazopanib vs. sunitinib was 0.91 (0.76-1.08). Similarly, bevacizumab with interferon, sunitinib, or pazopanib had better PFS and RR than interferon alone. Sunitinib and pazopanib had better RR than bevacizumab with interferon and there was suggestive evidence pazopanib may outperform sunitinib in terms of RR.
  
  
  CONCLUSIONS
  Bevacizumab with interferon, sunitinib, and pazopanib are adequate first-line options in treatment of mRCC. Interferon alone should not be considered an optimal first-line treatment.
authors.affiliation: Centre for Quantitative Medicine, Office of Clinical Sciences, Duke-National University of Singapore Graduate Medical School, 8 College Road, Singapore 169857, Singapore. ben.haaland@isye.gatech.edu.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Haaland
authors.forename: Akhil
authors.initials: A
authors.lastname: Chopra
authors.forename: Sanchalika
authors.initials: S
authors.lastname: Acharyya
authors.forename: André P
authors.initials: AP
authors.lastname: Fay
authors.forename: Gilberto de Lima
authors.initials: Gde L
authors.lastname: Lopes
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D006801:Humans; D007191:Indazoles; D007211:Indoles / Q000627:therapeutic use; D007372:Interferons / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy*; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D013449:Sulfonamides / Q000627:therapeutic use; D000077210:Sunitinib; D016019:Survival Analysis
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007191:Indazoles; D007211:Indoles; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D000068258:Bevacizumab; C516667:pazopanib; D007372:Interferons; D000077210:Sunitinib