Evaluation of progression-free survival as a surrogate endpoint for overall survival in locally advanced or metastatic differentiated thyroid cancer: a systematic review

Abstract

Purpose: Patients with locally advanced or metastatic differentiated thyroid cancer (DTC) have a variable prognosis, and the development of more effective treatment strategies is an important research topic. Overall survival (OS) is the gold standard for research endpoints in randomized controlled trials (RCTs), but observing an OS benefit requires the inclusion of a large number of patients and a long follow-up period. In this study, we aimed to investigate whether progression-free survival (PFS) could be used as a surrogate endpoint for OS in locally advanced or metastatic DTC clinical trials.

Materials and methods: We conducted a search in the PubMed and EMBASE databases to include all RCTs of locally advanced or metastatic DTC and extracted survival data. A weighted linear regression analysis was performed to explore the correlation between PFS benefit and OS benefit by taking the logarithm of the hazard ratios (HRs) of PFS and OS for each trial with a base of 10 and weighted by the number of patients in each RCT.

Results: Seven RCTs, including 1410 patients, were included. At the trial level, PFS benefit was weakly correlated with OS benefit (R² = 0.210, 95% CI: 0.000-0.811) and did not meet the statistical criteria for the surrogate endpoint.

Conclusion: This study does not support PFS as a surrogate endpoint for OS in locally advanced or metastatic DTC clinical trials.

Trial registration: PROSPERO Identifier: CRD42022334898.

Keywords: Differentiated thyroid cancer; Overall survival; Progression-free survival; Radioactive iodine refractory; Surrogate endpoint.