Progression-free survival (PFS) is often utilized as an indicator of the overall survival (OS) of patients with endometrial cancer (EC) to facilitate regulatory approval for novel medical treatments.¹ Nevertheless, its role as a surrogate marker for the survival outcomes of EC patients remains controversial among medical practitioners, with some questioning its reliability and suggesting its inability to reflect the eventual endpoint of the disease.¹ To investigate PFS surrogacy on OS among patients with recurrent and advanced EC, the European Organization For Research and Treatment of Cancer Young Gynaecologic Cancer Group (EORTC-YGCG) conducted a systematic review of randomized phase 2 and 3 clinical trials in advanced/recurrent EC.¹ During ESGO 2024 Congress,  Dr. Ramon Yarza from the Royal Marsden Hospital, London, the United Kingdom, shared the findings of this review.

In this systemic review, a total of 11,348 articles were screened and 11 articles that reported data on both PFS and OS were analyzed. 18 primary endpoints were presented, assessing PFS and OS in 7,784 patients.¹ Corresponding z-scores for standardized treatment benefits were estimated based on the hazard ratios (HRs) for OS and PFS.¹ Scatterplots of PFS z-scores (z-PFS) vs. OS z-scores (z-OS) were produced to indicate the regression intersect and Spearman’s correlation.¹ Furthermore, the surrogate threshold effect (STE) of PFS was determined based on the intersection point of the regression intersect In this systemic review, a total of 11,348 articles were screened and 11 articles that reported data on both PFS and OS were analyzed. 18 primary endpoints were presented, assessing PFS and OS in 7,784 patients.¹ Corresponding z-scores for standardized treatment benefits were estimated based on the hazard ratios (HRs) for OS and PFS.¹ Scatterplots of PFS z-scores (z-PFS) vs. OS z-scores (z-OS) were produced to indicate the regression intersect and Spearman’s correlation.¹ Furthermore, the surrogate threshold effect (STE) of PFS was determined based on the intersection point of the regression intersect with y=|log(0.05)|, representing α=0.05.¹ Subgroups analyses based on prior radiotherapy rates (≥50% and <50%) and prior lines of treatment (first-line and ≥2 lines) were also conducted.¹

The results of this systemic review demonstrated a moderate correlation between PFS and OS in the overall population (Spearman’s ρ=0.69; p=0.002), accompanied by a STE of 2.3 for z-PFS.¹ Subgroup analyses suggested more notable correlations between PFS and OS in trials with <50% prior radiotherapy (Spearman’s ρ=0.83; p=0.0014) and in first-line treatment trials (Spearman’s ρ=0.72; p=0.011), exhibiting a STE of 1.9 and 2.7, respectively.¹ Conversely, the correlation between PFS and OS remained insignificant in trials with ≥50% radiotherapy rates (p=0.33) and in second and subsequent-line  treatment trials (p=0.1).¹ However, a relatively low STE of 1.89 was observed in the subgroup analysis of the second and subsequent line treatment trials.¹

In summary, PFS was shown to be acceptable as a surrogate marker for OS, serving as a reliable tool for assessing EC treatment efficacy due to a relatively low STE for predicting OS outcomes in EC patients.¹ In particular, PFS surrogacy on OS was more pronounced in studies evaluating first-line treatments and in patient populations with lower prior radiotherapy rates, while the notably low STE in studies assessing second and subsequent treatments may suggest a potential PFS surrogacy on OS.¹