Time to deterioration of patient-reported outcomes as a surrogate of overall survival: a meta-analysis

Shahnam, A; Nindra, U; Desai, J; Hui, R; Buyse, M; Hopkins, AM; Sorich, MJ

Author(s): Shahnam, A; Nindra, U; Desai, J; Hui, R; Buyse, M; Hopkins, AM; Sorich, MJ;
Details: Publication Year 2023-08-04,Volume 115,Issue #12,Page 1475-1482
Journal Title: Journal of the National Cancer Institute
Publication Type: Research article
Abstract: BACKGROUND: Overall survival (OS) is the optimal marker of efficacy of treatments in randomized clinical trials (RCTs) but can take a considerable amount of time to mature. Progression free survival (PFS) has served as an early surrogate of OS however is imperfect. Time to deterioration (TTD) in quality of life (QoL) measures could be an alternative surrogate of OS. METHODS: Phase 3 RCTs in solid malignancies that reported OS, PFS and TTD in QoL or physical function (PF) published between 1st of January 2010 and 30th of June 2022 were evaluated. Weighted regression analysis was utilised to assess the relationship between PFS, TTD QoL and TTD PF with OS. The coefficient of determination (R2) was used to quantify surrogacy. RESULTS: 138 phase 3 RCT were included. 47 trials evaluated immune checkpoint inhibitors (ICIs) and 91 investigated non-ICI agents. TTD QoL (137 RCTs) and TTD PF (75 RCTs) performed similarly to PFS as surrogates of OS (R2 0.18 vs 0.19 and R2 0.10 vs 0.09, respectively). For ICI studies, TTD PF had a higher association with OS compared to PFS (R2 0.38 vs 0.19) and PFS and TTD PF were not correlated with each other (R2=0). When used together, the coefficient of determination increased (R2 = 0.57). CONCLUSIONS: TTD of PF appears to be a OS surrogate measure of particular importance for ICI treatment efficacy. The combination of TTD PF with PFS may enable better prediction of OS treatment benefit in ICI RCTs than either PFS or TTD PF alone.
Publisher: Oxford University Press
Department(s): Medical Oncology
PubMed ID: 37540222
Publisher's Version: https://doi.org/10.1093/jnci/djad152
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-11-21 05:54:31

Last Modified: 2024-09-05 06:55:57