title: Indirect treatment comparison of bevacizumab + interferon-α-2a vs tyrosine kinase inhibitors in first-line metastatic renal cell carcinoma therapy.
abstract: BACKGROUND
  The vascular endothelial growth factor inhibitor bevacizumab (BEV) given in combination with interferon-α-2a (IFN), and the tyrosine kinase inhibitors (TKIs) sunitinib (SUN) and pazopanib (PAZ), have all shown significant increase in progression-free survival (PFS) in first-line metastatic renal-cell carcinoma (mRCC) therapy. These targeted therapies are currently competing to be primary choice; hence, in the absence of direct head-to-head comparison, there is a need for valid indirect comparison assessment.
  
  
  METHODS
  Standard indirect comparison methods were applied to independent review PFS data of the pivotal Phase III trials, to determine indirect treatment comparison hazard-ratios (HR) with 95% confidence intervals (95% CI). As BEV+IFN and SUN have been compared to IFN, indirect comparison was enabled by the common IFN comparator arms. As PAZ was compared to placebo (PLA), a connector trial (IFN vs PLA) was required for the indirect comparison to BEV+IFN. Sensitivity analyses taking into account real-life influence of patient compliance on clinical outcomes were performed.
  
  
  RESULTS
  The indirect efficacy comparison resulted in a statistically nonsignificant PFS difference of BEV+IFN vs SUN (HR: 1.06; 95% CI: 0.78-1.45; P = 0.73) and of BEV+IFN vs PAZ (range based on different connector trials; HR: 0.74-1.03; P = 0.34-0.92). Simulating real-life patient compliance and its effectiveness impact showed an increased tendency towards BEV+IFN without reaching statistical significance.
  
  
  CONCLUSIONS
  There is no statistically significant PFS difference between BEV+IFN and TKIs in first-line mRCC. These findings imply that additional treatment decision criteria such as tolerability and therapy sequencing need to be considered to guide treatment decisions.
authors.affiliation: Department of Urology, Center of Operative Urology Bremen, Bremen, Germany;
authors.forename: Gerald Hj
authors.initials: GH
authors.lastname: Mickisch
authors.forename: Björn
authors.initials: B
authors.lastname: Schwander
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
authors.forename: José P
authors.initials: JP
authors.lastname: Maroto
authors.forename: Camillo
authors.initials: C
authors.lastname: Porta
authors.forename: Stefan
authors.initials: S
authors.lastname: Walzer
authors.forename: Uwe
authors.initials: U
authors.lastname: Siebert