Evaluation of complete response rate at 30 months (CR30) as a surrogate for progression-free survival (PFS) in first-line follicular lymphoma (FL) studies: Results from the prospectively specified Follicular Lymphoma Analysis of Surrogacy Hypothesis (FLASH) analysis with individual patient data (IPD) of 3,837 patients (pts).

Abstract

8504 Background: Although PFS is the standard endpoint for new drug approvals in first-line FL, advances in efficacy (median PFS >7 y) coupled with the indolent nature of FL necessitate extended patient follow-up in clinical trials. The FLASH group conducted a meta-analysis to evaluate whether treatment effects on CR30, an earlier endpoint, could accurately predict treatment effects on PFS. Methods: Correlation of CR30 odds ratio (OR) with PFS hazard ratio (HR) was evaluated using both linear regression (R2WLS) and copula bivariate (R2Copula) models. Prespecified criteria for CR30 surrogacy required either R2WLS or R2Copula ≥ 0.80 with a lower bound of the 95% confidence interval (CI) > 0.60, with neither estimate < 0.70. The minimum CR30 difference to predict significant PFS difference was calculated. Results: Data from 13 randomized first-line trials (8 induction, 5 maintenance trials) with IPD for 3837 pts were included. The prespecified threshold for surrogacy was met: R2WLS of 0.88 (95% CI, 0.77-0.96...