Meta-analysis to Investigate the Correlation Between Event-Free Survival and Overall Survival in Patients with...

While overall survival (OS) is a widely accepted trial endpoint in oncology, survival data are often immature in early-stage populations. Alternative time-to-event outcomes have been considered by regulatory and reimbursement agencies to allow for early patient access. Event-free survival (EFS) has shown strong correlations with OS in patients with locally advanced (LA) head and neck squamous cell carcinoma (HNSCC) and within the subgroup with unresectable tumors. With novel neoadjuvant and adjuvant immunotherapies being investigated in resectable LA-HNSCC, this study aimed to assess the trial-level correlation of EFS and OS in patients with resectable LA-HNSCC.

A systematic review (October 29, 2024) identified randomized controlled trials evaluating surgery with adjuvant therapy, neoadjuvant therapy, or both in patients with resectable LA-HNSCC. Trials reporting hazard ratios (HRs) or Kaplan-Meier curves for OS (time from randomization to death) and EFS (time from randomization to disease progression/recurrence or death) were eligible for the analysis. Base case included trials comparing neoadjuvant therapy + surgery + adjuvant therapy versus surgery + adjuvant therapy. Sensitivity analyses included models with trials comparing broader regimens (e.g., adjuvant therapy versus adjuvant therapy), excluding an outlier trial and restricting to publications after 2004. Correlations were measured between log(EFS HR) and log(OS HR) using regression models, with their strength measured using Pearson's correlation coefficient (R).

The review included 45 trials, with 20 trials qualifying for correlation analysis. R (95% confidence interval) was 0.91 (0.36, 0.99) in the base case (n = 5 trials) and 0.41 (-0.01, 0.71; n = 20), 0.78 (0.52, 0.91; n = 19), and 0.76 (0.41, 0.92; n = 13) in the three sensitivity analyses, respectively.

Strong trial-level correlations were observed between EFS and OS, suggesting EFS is a valid surrogate for OS in patients with resectable LA-HNSCC, particularly in trials investigating neoadjuvant therapy + surgery + adjuvant therapy.