Axitinib (AXI) and Everolimus (EVE) in the Treatment (TX) of Sunitinib-Refractory (SU-R) Patients (PTS) with Metastatic Renal Cell Carcinoma (MRCC): Results of a Simulated TX Comparison (STC) Analyses

ABSTRACT Background Axi is a novel VEGF targeted agent for mRCC pts who failed 1 prior systemic therapy. the The AXIS trial compared axi to sorafenib and showed a significantly longer PFS in pts treated with axi, including the su-r subgroup. No direct comparison is available between axi and eve but is an important clinical question. The goal of this analysis was to compare OS and PFS in su-r pts treated with axi and eve. Methods Pts who were su-r and received axi in the AXIS trial and eve in RECORD-1 trial were considered for this analysis. A STC method (Caro et al 2010) was used to derive OS and PFS curves for a hypothetical cohort of “axi like” pts had they received eve in the AXIS trial. Pt level AXIS data was used to derive predictive equations for OS and PFS. Parametric survival analysis identified the best fitting distribution and significant predictors of OS and PFS. These equations were calibrated using pt characteristics and median OS and PFS reported in the literature. Results 194 axi and 124 eve pts who were su-r were analyzed. While AXIS trial included only pts that progressed on 1 line of tx, 65% of su-r eve pts had 3 plus lines of therapy. Some pts were included in the eve trial without having progressed on 1st line tx. Available pt characteristics were comparable across two groups, except for difference in MSKCC risk categories (36% vs 17% poor risk pts in axi and eve respectively), mean duration of prior su (57 vs 44 weeks) and ECOG score (52% vs 60% with ECOG 0). A log-normal distribution provided the best fit for both OS and PFS. MSKCC risk category and duration of prior sunitinib were significant predictors of OS. The final PFS equation included MSKCC risk group and age. Estimated median OS and PFS was 15.2 and 5.1 months for axi compared to 10.6 and 3.6 months for eve group respectively. Estimated difference in mean OS and PFS between axi and eve was 7.6 and 2.6 months. Conclusion This analysis suggest that su-r RCC pts treated with axi may have an improved OS and PFS compared to pts treated with eve. Our analysis could not account for all differences between trials, such as number of prior therapies, however, a STC can provide additional comparative context. Disclosure I. Proskorovsky: I am an employee of United BioSource Corporation. As a research consulting organization, it received funding from Pfizer for the research undertaken in this abstract. A. Benedict: I am an employee of United BioSource Corporation. As a research consulting organization, it received funding from Pfizer for the research undertaken in this abstract. S. Negrier: Dr. Negrier has received honorariums from Pfizer and Novartis as well as research grants from GlaxoSmithKline and Roche. J. Larkin: research funding from Pfizer and Novartis, advisory role to Pfizer, Novartis, GSK, BMS, Aveo. R. Sandin: Employee of Pfizer AB. Stock or other ownership interests in Pfizer Inc. C. Chen: Employee and stockholder of Pfizer only