Progression-free survival as a surrogate for overall survival in ovarian cancer: Real-world evidence-based assessment and trial-level correlation.

Abstract

e17587 Background: Progression-free survival (PFS) is widely used as a surrogate endpoint for overall survival (OS) in ovarian cancer, but its validity varies across clinical contexts. To evaluate PFS–OS surrogacy using individual-level agreement in a large real-world cohort and trial-level correlation across randomized studies. Methods: An institutional cohort of 4,269 patients was analyzed to compare factor-specific hazard ratios (HRs) for PFS and OS and to quantify individual-level surrogacy using censored Kendall’s τ. Trial-level HRs were extracted from phase II/III ovarian cancer trials. Surrogacy was assessed using Spearman correlation, Bland–Altman agreement, and weighted meta-regression, with stratified analyses by disease setting, treatment modality, publication era, maintenance therapy, and HR_PFS thresholds. Results: In the institutional cohort, HR_PFS and HR_OS showed near-perfect concordance (R = 0.98) with minimal bias. Censored Kendall’s τ indicated strong individual-level correlation (τ = 0.78; p < 0.001), with 89% concordant event ordering. Across trials, PFS and OS demonstrated moderate correlation (ρ ≈ 0.62) with small mean bias but wide limits of agreement. Surrogacy was strongest in platinum-resistant disease and first-line cytotoxic chemotherapy, and weaker in platinum-sensitive and targeted therapy settings. Maintenance-therapy trials showed more stable agreement than non-maintenance trials. Temporal analyses revealed the most robust surrogacy in the 2010s, with attenuation in the 2020s as treatment heterogeneity increased. Conclusions: PFS is a practical but context-dependent surrogate for OS in ovarian cancer. Strong individual-level and HR-level concordance supports its use, although trial-level surrogacy varies by disease setting, treatment modality, and therapeutic era. Continued validation is essential as modern treatments reshape post-progression outcomes.