Real-World Evidence Prediction of a Phase IV Oncology Trial: Comparative Degarelix vs Leuprolide Safety

Abstract

Abstract Background Medical and regulatory communities are increasingly interested in the utility of real-world evidence (RWE) for answering questions pertaining to drug safety and effectiveness, but concerns about validity remain. A principled approach to conducting RWE studies may alleviate concerns and increase confidence in findings. This study sought to predict the findings from the PRONOUNCE trial using a principled approach to generating RWE. Methods This propensity score–matched observational cohort study used 3 claims databases to compare the occurrence of major adverse cardiovascular events among initiators of degarelix vs leuprolide. Patients were included if they had a history of prostate cancer and atherosclerotic cardiovascular disease. Patients were excluded if they did not have continuous database enrollment in the year before treatment initiation, were exposed to androgen deprivation therapy or experienced an acute cardiovascular event within 30 days before treatment initiation, or had a history or risk factors of QT prolongation. Results There were 12 448 leuprolide and 1969 degarelix study-eligible patients before matching, with 1887 in each arm after propensity score matching. The results for major adverse cardiovascular events comparing degarelix with leuprolide in the observational analysis (hazard ratio = 1.35, 95% confidence interval = 0.94 to 1.93) was consistent with the subsequently released PRONOUNCE result (hazard ratio = 1.28, 95% confidence interval  = 0.59 to 2.79). Conclusions This study successfully predicted the result of a comparative cardiovascular safety trial in the oncology setting. Although the findings are encouraging, limitations of measuring cancer stage and tumor progression are representative of challenges in attempting to generalize whether claims-based RWE can be used as actionable evidence.