Association Between Intermediate End Points, Progression-free Survival, and Overall Survival in First-line Advanced or Recurrent Endometrial Cancer

Abstract

Purpose: Advanced/recurrent endometrial cancer is associated with poor long-term outcomes. Clinical studies of novel regimens are ongoing, but given that data on overall survival (OS) take a long time to mature, surrogate end points are often used to support clinical-research interpretation. The aim of this study was to explore the correlation between progression-free survival (PFS)/time to progression (TTP) and OS across multiple time points in the first-line treatment of advanced/recurrent endometrial cancer.

Methods: This study comprised meta-analyses of Phase 2/3 randomized, controlled trials of first-line treatments in patients with advanced primary or first-recurrent endometrial cancer identified via systematic literature review. The strength of the surrogacy relationship was assessed by correlation analyses (estimated with Spearman and Pearson correlation coefficients) and weighted linear regression.

Findings: Data from 15 studies were included. PFS and TTP (TTP was reported in one study only) were highly correlated with future OS at multiple time points (Spearman values, 0.83-0.90; Pearson values, 0.86-0.93), suggesting that a change in PFS/TTP would likely be correlated with a change in OS in the same direction. On weighted linear regression, a 10% increase in PFS/TTP probability was significantly associated with a 9.3% to 13.3% increase in the probability of future OS. The strong positive association between PFS/TTP and OS was supported by findings from sensitivity analyses based on identified sources of interstudy heterogeneity.

Implications: PFS/TTP is a good potential candidate for predicting long-term OS outcomes in trials of first-line treatment in patients with advanced/recurrent endometrial cancer. The findings from this report may help to inform health-authority and clinical decision makers that PFS/TTP improvements are likely to translate into subsequent OS improvements once data mature.

Keywords: Endometrial cancer; Intermediate end points; Outcomes; Overall survival; Progression-free survival; Surrogate end points; Time to progression.