Validation of Progression-Free Survival as a Surrogate Endpoint for Overall Survival in Malignant Mesothelioma: Analysis of Cancer and Leukemia Group B and North Central Cancer Treatment Group (Alliance) Trials.

TitleValidation of Progression-Free Survival as a Surrogate Endpoint for Overall Survival in Malignant Mesothelioma: Analysis of Cancer and Leukemia Group B and North Central Cancer Treatment Group (Alliance) Trials.
Publication TypeJournal Article
Year of Publication2017
AuthorsWang, Xiaofei, Xiaoyi Wang, Lydia Hodgson, Stephen L. George, Daniel J. Sargent, Nate R. Foster, Apar Kishor Ganti, Thomas E. Stinchcombe, Jeffrey Crawford, Robert Kratzke, Alex A. Adjei, Hedy L. Kindler, Everett E. Vokes, and Herbert Pang
JournalOncologist
Volume22
Issue2
Pagination189-198
Date Published2017 02
ISSN1549-490X
KeywordsAdult, Aged, Aged, 80 and over, Disease-Free Survival, Female, Humans, Lung Neoplasms, Male, Mesothelioma, Mesothelioma, Malignant, Middle Aged, Survival Analysis, Young Adult
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 HR and log HR-measured in from a weighted least-square (WLS) regression model and the CBCS model.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 ranged from 0.51 for PS to 0.78 for histology. The WLS 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. 2017;22:189-198 For better disease management and for more efficient clinical trial designs, it is important to know if progression-free survival (PFS) is a good surrogate endpoint for overall survival in malignant mesothelioma. With a relatively large database of 17 phase II trials and 716 patients from Cancer and Leukemia Group B and North Central Cancer Treatment Group, we conducted statistical analyses and found that there is no evidence to suggest that PFS is a valid surrogate endpoint for OS for malignant mesothelioma. Future research work is needed to find alternative surrogate endpoints for OS.

DOI10.1634/theoncologist.2016-0121
Alternate JournalOncologist
Original PublicationValidation of progression-free survival as a surrogate endpoint for overall survival in malignant mesothelioma: Analysis of Cancer and Leukemia Group B and North Central Cancer Treatment Group (Alliance) Trials.
PubMed ID28188257
PubMed Central IDPMC5330706
Grant ListU10 CA033601 / CA / NCI NIH HHS / United States
R21 AG042894 / AG / NIA NIH HHS / United States
U10 CA180821 / CA / NCI NIH HHS / United States
U10 CA180836 / CA / NCI NIH HHS / United States
U10 CA180857 / CA / NCI NIH HHS / United States
U10 CA180882 / CA / NCI NIH HHS / United States
P01 CA142538 / CA / NCI NIH HHS / United States
U10 CA180838 / CA / NCI NIH HHS / United States
U10 CA180866 / CA / NCI NIH HHS / United States