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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.

Publication ,  Journal Article
Wang, X; Wang, X; Hodgson, L; George, SL; Sargent, DJ; Foster, NR; Ganti, AK; Stinchcombe, TE; Crawford, J; Kratzke, R; Adjei, AA; Kindler, HL ...
Published in: Oncologist
February 2017

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 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 R2 ranged from 0.51 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. The Oncologist 2017;22:189-198Implications for Practice: 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.

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Published In

Oncologist

DOI

EISSN

1549-490X

Publication Date

February 2017

Volume

22

Issue

2

Start / End Page

189 / 198

Location

England

Related Subject Headings

  • Young Adult
  • Survival Analysis
  • Oncology & Carcinogenesis
  • Middle Aged
  • Mesothelioma, Malignant
  • Mesothelioma
  • Male
  • Lung Neoplasms
  • Humans
  • Female
 

Citation

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Wang, X., Hodgson, L., George, S. L., Sargent, D. J., Foster, N. R., Ganti, A. K., … Pang, H. (2017). 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. Oncologist, 22(2), 189–198. https://doi.org/10.1634/theoncologist.2016-0121
Wang, Xiaofei, Xiaoyi Wang, Lydia Hodgson, Stephen L. George, Daniel J. Sargent, Nate R. Foster, Apar Kishor Ganti, et al. “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.Oncologist 22, no. 2 (February 2017): 189–98. https://doi.org/10.1634/theoncologist.2016-0121.
Wang X, Hodgson L, George SL, Sargent DJ, Foster NR, Ganti AK, Stinchcombe TE, Crawford J, Kratzke R, Adjei AA, Kindler HL, Vokes EE, Pang H. 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. Oncologist. 2017 Feb;22(2):189–198.

Published In

Oncologist

DOI

EISSN

1549-490X

Publication Date

February 2017

Volume

22

Issue

2

Start / End Page

189 / 198

Location

England

Related Subject Headings

  • Young Adult
  • Survival Analysis
  • Oncology & Carcinogenesis
  • Middle Aged
  • Mesothelioma, Malignant
  • Mesothelioma
  • Male
  • Lung Neoplasms
  • Humans
  • Female