Presentation (CTI)

OBJECTIVES: Although OS is the gold-standard endpoint in oncology, survival data are often immature in trials in early-stage populations, and regulatory agencies have accepted alternative time-to-event outcomes to allow for early patient access. EFS has been shown to have a strong correlation with OS in the overall LA-HNSCC population and within the subgroup with unresectable tumors. Novel neoadjuvant and adjuvant immunotherapies are emerging in the treatment landscape of solid cancers, including resectable HNSCC. This study aimed to assess the trial-level association of EFS and OS in patients with resectable LA-HNSCC.
METHODS: A systematic literature review (April 29, 2024) identified randomized controlled trials evaluating neoadjuvant and/or adjuvant therapies in newly-diagnosed LA-HNSCC patients receiving surgery. 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. The base case was restricted to trials comparing neoadjuvant+surgery±adjuvant therapies to surgery±adjuvant therapies. Sensitivity analyses #1, #2, and #3 included trials comparing broader regimens (e.g., adjuvant therapy vs. adjuvant therapy), excluded outlier trials, and restricted to trials published in or after 2005, respectively. Correlations were measured between log (EFS HR) and log (OS HR) using regression models, with their strengths evaluated using Pearson’s correlation coefficient (R). Models were validated using leave-one-out analyses.
RESULTS: The systematic review included 19 trials. R (95% confidence interval) was estimated as 0.91 (0.36, 0.99) for the base case (n=5 trials) and as 0.41 (-0.03, 0.71), 0.78 (0.52, 0.91), and 0.76 (0.39, 0.92) for sensitivity analyses #1 (n=19), #2 (n=18), and #3 (n=12), respectively. Models predicted OS HRs accurately in the leave-one-out analyses.
CONCLUSIONS: Moderate-to-strong associations were observed between EFS and OS, suggesting EFS is a valid surrogate for OS in newly-diagnosed patients with resectable LA-HNSCC, particularly in trials investigating neoadjuvant+surgery±adjuvant therapies.