Validation of progression-free survival as a surrogate endpoint for overall survival inmalignant mesothelioma: Analysis of cancer and leukemia group B and north central cancer treatment group (Alliance) trials

Xiaofei Wang, Xiaoyi Wang, Lydia Hodgson, Stephen L. George, Daniel J. Sargent, Nate R. Foster, Apar Kishor Ganti, Thomas E. Stinchcombe, Jeffrey Crawford, Robert Kratzke, Alex Adjei, Hedy L. Kindler, Everett E. Vokes, Herbert Pang

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Purpose. The aim of this study was to investigate whether progression-free survival (PFS) can be considered a surrogate endpoint for overall survival (OS) in malignant mesothelioma. Materials and Methods. Individual data were collected from 15 Cancer and Leukemia Group B (615 patients) and 2 North Central Cancer Treatment Group (101 patients) phase II trials. The effects of 5 risk factors for OS and PFS, including age, histology, performance status (PS), white blood cell count, and European Organisation for Research and Treatment of Cancer (EORTC) risk score, were used in the analysis. Individual-level surrogacy was assessed by Kendall’s tau through a Clayton bivariate Copula survival (CBCS) model. Summary-level surrogacy was evaluated via the association between logarithms of the hazard ratio (log HR)—log HROS and log HRPFS—measured in R2 from a weighted least-square (WLS) regression model and the CBCSmodel. Results. The median PFS for all patients was 3.0 months (95% confidence interval [CI], 2.8–3.5 months) and the median OS was 7.2 months (95% CI, 6.5–8.0 months). Moderate correlations between PFS and OS were observed across all risk factors at the individual level, with Kendall’s tau ranging from 0.46 to 0.47. The summary-level surrogacy varied among risk factors. The Copula R2 ranged from0.51 for PS to 0.78 for histology. The WLS R2 ranged from 0.26 for EORTC and PS to 0.67 for age. Conclusions. The analyses demonstrated low to moderate individual-level surrogacy between PFS and OS. At the summary level, the surrogacy between PFS and OS varied significantly across different risk factors. With a short postprogression survival and a moderate correlation between PFS and OS, there is no evidence that PFS is a valid surrogate endpoint for OS in malignant mesothelioma.

Original languageEnglish (US)
Pages (from-to)189-198
Number of pages10
JournalOncologist
Volume22
Issue number2
DOIs
StatePublished - Feb 10 2017

    Fingerprint

Keywords

  • Malignant mesothelioma
  • Overall survival
  • Progression-free survival
  • Risk factors
  • Surrogate endpoint

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Wang, X., Wang, X., Hodgson, L., George, S. L., Sargent, D. J., Foster, N. R., Ganti, A. K., Stinchcombe, T. E., Crawford, J., Kratzke, R., Adjei, A., Kindler, H. L., Vokes, E. E., & Pang, H. (2017). Validation of progression-free survival as a surrogate endpoint for overall survival inmalignant mesothelioma: Analysis of cancer and leukemia group B and north central cancer treatment group (Alliance) trials. Oncologist, 22(2), 189-198. https://doi.org/10.1634/theoncologist.2016-0121