Indirect treatment comparison of bevacizumab + interferon-α-2a vs tyrosine kinase inhibitors in first-line metastatic renal cell carcinoma therapy

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.