Adjusted indirect comparison of everolimus and sorafenib in sunitinib-refractory mRCC patients using a robust matching technique.

Abstract

378 Background: Vascular endothelial growth factor receptor–tyrosine kinase inhibitors (VEGFr-TKIs) sunitinib (SU) and sorafenib (SO) are approved for first- and second-line (after cytokines) use in metastatic renal cell carcinoma (mRCC). Because most patients progress after first-line VEGFr-TKI, the need for an effective second-line treatment is compelling. Although SO is frequently considered after SU failure, no randomized controlled trials have established clinical benefit in this scenario. Results from the RECORD-1 phase III trial suggest that second-line everolimus (EVE) therapy leads to improved overall survival (OS) vs. placebo. No trial data exist comparing treatment outcomes for EVE vs SO in the second-line setting. Thus, the current analysis provides a robust estimate from an indirect comparison examining the OS benefit of EVE and SO as second-line treatment options after SU failure. Methods: The single-arm SO study was selected as a basis by which to match an EVE SU-refractory subpopulation of the RECORD-1 trial. Patients were limited to those with clear cell histology. An adjusted matching approach was taken in which 1,000 repeated random samples matched to the SO population on risk score distribution were produced. These data were used to generate a distribution of survival outcomes and infer a 95% CI around the mean of all sampled median OS estimates. Results: After adjusted matching, the estimated median OS benefit, based on SO patients with clear cell histology (n = 45) and 1000 random samples of n = 41 from the 127 SU-refractory EVE patients, was 82 weeks (95% CI: 78, 86) and 32 weeks (95% CI: 22, 64) for EVE and SO, respectively. Conclusions: These indirect comparison results suggest that SU-refractory mRCC patients treated with EVE may experience significantly improved OS outcomes compared with patients treated with SO. [Table: see text]