Journal Article

DKFZ-2025-02961

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Benchmarking progression-free survival ratio as primary endpoint in precision oncology clinical trials.

Nichetti, F. (First author)DKFZ* ; Hüllein, J. (First author)DKFZ* ; du Rusquec, P. ; Pleasance, E. ; Chen, L. ; Mock, A. ; Horak, P.DKFZ* ; Ambrosini, P. ; Rota, S. ; Niger, M. ; Agnelli, L. ; Tinè, G. ; Edelmann, D.DKFZ* ; Le Tourneau, C. ; Laskin, J. ; Pruneri, G. ; Wang, C. ; Hübschmann, D.DKFZ* ; de Braud, F. ; Fröhling, S. (Last author)DKFZ* ; Mariani, L.

2025
Springer Nature [London]

Abstract: 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) from >800 patients revealed an overall weak PFS1/PFS2 correlation (Kendall's τ range 0.17-0.35), and an asymptotically unbiased median SPFSratio(δ=1.3) = 33% by means of the Kernel-based analysis, while other methods considerably deviated in studies with censoring rate>10%. This methodology is implemented in the PROPHETS R package and Shiny app.

Note: #EA:B340#LA:B340# / epub

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Contributing Institute(s):

1. Translationale Medizinische Onkologie (B340)
2. DKTK HD zentral (HD01)
3. C060 Biostatistik (C060)
4. Innovations- und Service-Unit für Bioinformatik und Präzisionsmedizin (W015)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2025

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Database coverage:
; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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