Background: The phase III, double-blind, placebo-controlled RECORD-1 trial (NCT00410124) evaluated everolimus (EVE) in VEGF receptor-tyrosine kinase inhibitor (VEGFr-TKI) refractory mRCC. An updated intent-to-treat OS analysis favored EVE (hazard ratio [HR]=0.87, 95% CI: 0.65- 1.15, p=0.162), but was likely null biased as a result of crossover of ~80% of placebo (PLB) patients to EVE treatment. These 2 validated and independentmethods were used to correct OS for crossover and estimate true survival benefit of a therapy vs PLB had there been no crossover. Methods: RPSFT postulates a structural model where each day on EVE (whether randomized to EVE or after crossover) prolongs survival by a multiplicative factor. The RPSFT method respects randomization and provides a crossover-corrected estimate. The weighted marginal structural IPCW Cox proportional hazards model uses pooled logistic regressions to estimate weights equal to the inverse probability of not crossing over (ie, the probability of PLB patients remaining not censored) and applies these to the final Cox model, resulting in a HR measure of effect. Multiple models were examined using alternate methods to segment time to identify baseline and time-dependent covariates for inclusion. Results: RPSFT estimated survival time was 1.9-fold longer (95% CI: 0.5-8.5) with EVE vs PLB (ie, hypothetical PLB without crossover). A corrected PLB Kaplan-Meier curve estimated OS at 10.0 mo (observed was 14.4 mo). OS for patients randomized to EVE was 14.8 mo. OS HR estimates from multiple IPCW Cox models were robust and indicated a benefit for EVE. Estimated HRs ranged from 0.44-0.55 and most estimated treatment effects were statistically significant. Point estimates from the RPSFT and IPCW methods are intuitively comparable as the former suggests a roughly 2 times longer survival on EVE and the latter suggest a roughly 50% reduction in death risk. Conclusions: Both independent crossover correction methods suggest that EVE was associated with an OS benefit in VEGFr-TKI refractory mRCC patients in RECORD-1.