PCN8 Axitinib (AXI) and Best Supportive Care (BSC) in the Treatment of Sunitinib-Refractory Patients With Metastatic Renal Cell Carcinoma (mRCC): Results of a Simulated Treatment Comparison (STC) Analyses

To compare overall survival (OS) and progression free survival (PFS) in sunitinib-refractory (SU-r) patients with mRCC treated with AXI and BSC using STC. STC method was used to derive OS and PFS curves for a hypothetical cohort of “AXI-like” patients had they received BSC in the AXIS trial. Patient level data on SU-r patients from the AXIS trial were 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 patient characteristics and mPFS and cross-over adjusted mOS of the BSC cohort in the RECORD-1 trial. In AXIS all 194 SU-r AXI patients progressed on one line of treatment. In RECORD-1 78% of BSC patients had 2+ prior lines and some failed 1st line treatment due to intolerability. Other available patient characteristics were comparable except for MSKCC risk category (36% vs 15% poor risk, AXI vs BSC respectively) and ECOG score (52% vs 68% with ECOG 0). The final predictive equations using the best-fitting log-normal distribution included MSKCC risk group and age for PFS, and MSKCC risk category and duration of prior SU for OS. Median estimated OS and PFS was 15.2 and 5.1 months for AXI compared to 8.3 and 1.6 months for BSC respectively. Estimated difference in mean OS and PFS between AXI and BSC was 11.4 and 5.9 months. Sensitivity analyses using patient characteristics of the SU-r subgroup of everolimus arm and Weibull distribution showed similar results. The STC analysis, an alternative to mixed treatment comparison, suggested a significant improvement in OS and PFS for SU-r mRCC patients treated with AXI compared to BSC. However, the analysis could not account for all the differences between patient populations, particularly for the number of prior non-VEGFR-TKI therapies.