Event-Free Survival, a Prostate-Specific Antigen-Based Composite End Point, Is Not a Surrogate for Overall Survival in Men With Localized Prostate Cancer Treated With Radiation.

Xie, Wanling, Regan, Meredith M, Buyse, Marc, Halabi, Susan, Kantoff, Philip W, Sartor, Oliver, Soule, Howard, Berry, Donald, Clarke, Noel, Collette, Laurence, D'Amico, Anthony, Lourenco, Richard De Abreu, Dignam, James, Eisenberger, Mario, James, Nicholas D, Fizazi, Karim, Gillessen, Silke, Loriot, Yohann, Mottet, Nicolas, Parulekar, Wendy, Sandler, Howard, Spratt, Daniel E, Sydes, Matthew R, Tombal, Bertrand, Williams, Scott and Sweeney, Christopher J (2020) Event-Free Survival, a Prostate-Specific Antigen-Based Composite End Point, Is Not a Surrogate for Overall Survival in Men With Localized Prostate Cancer Treated With Radiation. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. JCO1903114. ISSN 1527-7755. This article is available to all UHB staff and students via Ask Discovery http://tinyurl.com/z795c8c by using their UHB Athens login IDs

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Official URL: https://ascopubs.org/journal/jco

Abstract

PURPOSE

Recently, we have shown that metastasis-free survival is a strong surrogate for overall survival (OS) in men with intermediate- and high-risk localized prostate cancer and can accelerate the evaluation of new (neo)adjuvant therapies. Event-free survival (EFS), an earlier prostate-specific antigen (PSA)-based composite end point, may further expedite trial completion.

METHODS

EFS was defined as the time from random assignment to the date of first evidence of disease recurrence, including biochemical failure, local or regional recurrence, distant metastasis, or death from any cause, or was censored at the date of last PSA assessment. Individual patient data from trials within the Intermediate Clinical Endpoints in Cancer of the Prostate-ICECaP-database with evaluable PSA and disease follow-up data were analyzed. We evaluated the surrogacy of EFS for OS using a 2-stage meta-analytic validation model by determining the correlation of EFS with OS (patient level) and the correlation of treatment effects (hazard ratios [HRs]) on both EFS and OS (trial level). A clinically relevant surrogacy was defined a priori as an ≥ 0.7.

RESULTS

Data for 10,350 patients were analyzed from 15 radiation therapy-based trials enrolled from 1987 to 2011 with a median follow-up of 10 years. At the patient level, the correlation of EFS with OS was 0.43 (95% CI, 0.42 to 0.44) as measured by Kendall's tau from a copula model. At the trial level, the was 0.35 (95% CI, 0.01 to 0.60) from the weighted linear regression of log(HR)-OS on log(HR)-EFS.

CONCLUSION

EFS is a weak surrogate for OS and is not suitable for use as an intermediate clinical end point to substitute for OS to accelerate phase III (neo)adjuvant trials of prostate cancer therapies for primary radiation therapy-based trials.

Item Type: Article
Additional Information: This article is available to all UHB staff and students via Ask Discovery http://tinyurl.com/z795c8c by using their UHB Athens login IDs
Subjects: QZ Pathology. Oncology
W Public health. Health statistics. Occupational health. Health education
WD Diseases and disorders of systemic, metabolic or environmental origin
WD Diseases and disorders of systemic, metabolic or environmental origin > WD250 Metabolic diseases
WJ Urogenital system. Urology
Divisions: Planned IP Care > Oncology and Clinical Haematology
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Depositing User: Jamie Edgar
Date Deposited: 08 Jul 2020 09:54
Last Modified: 08 Jul 2020 09:54
URI: http://www.repository.uhblibrary.co.uk/id/eprint/3230

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