biostudies-literatureNichetti FNCI NIH HHS38https://www.ebi.ac.uk/biostudies/studies/S-EPMC12820104biostudies-literatureUnknown10(1)Progression Free Survival Ratio (PFSratio), as defined as the ratio between PFS on investigational treatment (PFS2) and PFS on the last prior therapy (PFS1), is a popular endpoint in precision oncology (PO) studies. In this work, five methodologies for PFSratio-based trial analysis (count-based, Kaplan Meier, Kernel-based Kaplan Meier, parametric and midrank) and two for trial design (GBVE and Weibull) are benchmarked. The Kernel-based Kaplan Meier analysis is most recommended, as it handles informative censoring and does not require PFS1/PFS2 distribution assumptions. Sample size and power calculation methods perform best when applied to settings with expected high PFS1/PFS2 correlation and median ratio. Analysis of five clinical trials (MOSCATO 01, WINTHER, MASTER, SHIVA and POG570) fromNPJ precision oncologyBenchmarking progression-free survival ratio as primary endpoint in precision oncology clinical trials.PMC12820104R21 CA284179R21CA284179-01A1Tine Gde Braud FRota SMock AHubschmann DWang CChen LNichetti FNiger MAmbrosini PFrohling SHullein JPruneri GLe Tourneau CLaskin JEdelmann DMariani LPleasance EHorak PAgnelli Ldu Rusquec PfalseBenchmarking progression-free survival ratio as primary endpoint in precision oncology clinical trials.Progression Free Survival Ratio (PFSratio), as defined as the ratio between PFS on investigational treatment (PFS2) and PFS on the last prior therapy (PFS1), is a popular endpoint in precision oncology (PO) studies. In this work, five methodologies for PFSratio-based trial analysis (count-based, Kaplan Meier, Kernel-based Kaplan Meier, parametric and midrank) and two for trial design (GBVE and Weibull) are benchmarked. The Kernel-based Kaplan Meier analysis is most recommended, as it handles informative censoring and does not require PFS1/PFS2 distribution assumptions. Sample size and power calculation methods perform best when applied to settings with expected high PFS1/PFS2 correlation and median ratio. Analysis of five clinical trials (MOSCATO 01, WINTHER, MASTER, SHIVA and POG570) from2025-01-01T00:00:00Z2025 Dec2026-07-15T09:10:24.016Z2026-07-02T03:08:52.579ZS-EPMC128201044139805310.1038/s41698-025-01231-x