A Weighted-Adjusted Indirect Comparison Of Everolimus (Eve) Versus Axitinib (Axi) In Second-Line Metastatic Renal Cell Carcinoma (Mrcc) Patients Who Previously Failed Sunitinib Therapy.

491 Background: Both EVE and AXI have been approved for second-line treatment of mRCC after VEGFR-TKI therapy failure. No head-to-head clinical trial has compared clinical outcomes between EVE and AXI in this setting. This study aims to compare progression free survival (PFS) from two phase III clinical trials among mRCC patients with SUN as their only prior antineoplastic therapy and subsequently treated with EVE in the RECORD-1 trial vs. AXI in the AXIS trial, after adjusting for cross-trial differences. Methods: A weighted-adjusted indirect comparison using patient-level data from RECORD-1 and summary data from the AXIS trial publication was performed to align baseline characteristics from both trials and compare PFS (central review). A subset of N=43 second-line SUN -refractory mRCC patients treated with EVE were identified in RECORD-1 to correspond to a similar subset of patients (N=194) treated with AXI in AXIS. Logistic regression was used to identify factors predicting PFS in RECORD-1. The RECORD-1 subset was weighted to align the distributions of these key factors (i.e., MSKCC risk, gender, and time on prior SUN) with the AXIS subset. Weights were calculated for each patient using the following equation: W i = [P i (A AXIS )/P i (A RECORD-1 )] * [P i (B AXIS )/P i (B RECORD-1 )] * [P i (C AXIS )/P i (C RECORD-1 )], where A=Gender, B=MSKCC risk, and C=time on prior SUN. A weighted median PFS estimate with 95% bootstrap confidence interval (CI) and corresponding Kaplan-Meier (KM) curve were derived for EVE patients. Results: After weighting, the three key baseline characteristics were mostly comparable between the two studies, with the exception of MSKCC where a higher proportion of poor risk patients was evident in RECORD-1 (42%) vs. AXIS (33%). A median PFS of 5.1 months (95% CI: 3.6-10.7) was observed for weighted EVE patients compared to 4.8 months (95% CI: 4.5-6.4) reported in AXIS. Conclusions: The PFS estimates suggest similar efficacy between EVE and AXI in SUN-refractory mRCC patients. Further research is needed to confirm these results, which should be interpreted as those from an observational study.