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Abstract
Introduction/Background Progression-Free Survival (PFS) as a surrogate marker for Overall Survival (OS) has been a topic of debate. PFS poses challenges in capturing the true endpoint, as it only accounts for a limited period of the disease. To address this issue, we investigated the surrogacy of PFS for OS among recurrent/advanced endometrial cancer (EC) trials.
Methodology We systematically reviewed randomized phase 2 and 3 clinical trials in advanced/recurrent EC, following PRISMA guidelines, with inclusion criteria based on mature PFS and OS data. We excluded trials reporting recurrence-free survival or disease-free survival. The primary endpoint was to assess overall surrogacy of PFS on OS outcomes among all trials. We estimated standardized treatment benefits using Wald statistics (z-scores) based on Hazard Ratios for OS and PFS. Exploratory analyses comprised cohorts with ≥50% or <50% prior radiotherapy and trials exploring first-line systemic treatment versus ≥2 lines of prior therapy. PROSPERO registration: CRD42023405604.
Results Out of 11,348 screened articles 238 were deemed for full-text screening and 11 were included in our final analysis. We detected a moderate correlation between PFS and OS (Spearman’s rho = 0.69; p-value = 0.0022). Additionally, a Surrogate Threshold Effect (STE) with a z-score of 2.3 was identified, suggesting a low intersection point between the surrogate and the significant threshold for OS at α= 0.05. Sub-analyses revealed stronger correlations in trials with <50% prior radiotherapy (Spearman’s rho = 0.83, p-value = 0.0014) and in first-line systemic treatment trials (Spearman’s rho = 0.72, p-value = 0.011). In contrast, no statistical significance was observed in trials with higher prior radiotherapy rates or those assessing second and subsequent lines of systemic treatment, despite limited sample size.
Conclusion PFS is an acceptable surrogate marker for OS to assess treatment efficacy in EC trials, showing a low STE to further predict a meaningful OS benefit.
Disclosures Dr. Madariaga reports consultation fees from GSK, AstraZeneca and PharmaMar;participation in company sponsored speaker’s bureau for GSK, AstraZeneca, Clovis and MSD. Dr. Herrera reports research supports from Accuray inc, Bioprotect, Bristol-Myers Squibb, Roche-ImFlame/ImCore, Nanobiotix, TherAGuIX, AstraZeneca, Eisai, MSD, SeagenProstate Cancer FoundationSan Salvatore FoundationBiltema Foundation; consultation fees from Johnson & Johnson, Boehringer Ingelheim,Seagen, MSD, Bristol-Myers Squibb, AstraZeneca, Eisai; participation in a company sponsored speaker’s bureau: Johnson & Johnson, Boehringer Ingelheim,Seagen, MSD, Bristol-Myers Squibb, AstraZeneca, Eisai. Dr. Kroep reports research supports from Dutch Cancer Society, WCRF, AstraZeneca, Novartis, Philips; consultation fees from AstraZeneca, Elli Lilly, GSK, MSD, Novartis. The rest of the authors have no COIs to report.
