Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/46298
Title: Validation of metastasis-free survival as a surrogate endpoint for overall survival in localized prostate cancer in the era of docetaxel for castration-resistant prostate cancer
Authors: Xie, W
Ravi, P
BUYSE, Marc 
Halabi, S
Kantoff, P
Sartor, O
Soule, H
Clarke, N
Dignam, J
James, N
Fizazi, K
Gillessen, S
Mottet, N
Murphy , L
Parulekar, W
Sandler, H
Tombal, B
Williams, S
Sweeney, CJ
Issue Date: 2024
Publisher: ELSEVIER
Source: Annals of oncology, 35 (3) , p. 285 -292
Abstract: Background: Prior work from the Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) consortium (ICECaP-1) demonstrated that metastasis-free survival (MFS) is a valid surrogate for overall survival (OS) in localized prostate cancer (PCa). This was based on data from patients treated predominantly before 2004, prior to docetaxel being available for the treatment of metastatic castrate-resistant prostate cancer (mCRPC). We sought to validate surrogacy in a more contemporary era (ICECaP-2) with greater availability of docetaxel and other systemic therapies for mCRPC. Patients and methods: Eligible trials for ICECaP-2 were those providing individual patient data (IPD) after publication of ICECaP-1 and evaluating adjuvant/salvage therapy for localized PCa, and which collected MFS and OS data. MFS was defined as distant metastases or death from any cause, and OS was defined as death from any cause. Surrogacy was evaluated using a meta-analytic two-stage validation model, with an R-2 >= 0.7 defined a priori as clinically relevant. Results: A total of 15 164 IPD from 14 trials were included in ICECaP-2, with 70% of patients treated after 2004. The median follow-up was 8.3 years and the median postmetastasis survival was 3.1 years in ICECaP-2, compared with 1.9 years in ICECaP-1. For surrogacy condition 1, Kendall's tau was 0.92 for MFS with OS at the patient level, and R-2 from weighted linear regression (WLR) of 8-year OS on 5-year MFS was 0.73 (95% confidence interval 0.53-0.82) at the trial level. For condition 2, R-2 was 0.83 (95% confidence interval 0.64-0.89) from WLR of log[hazard ratio (HR)]OS on log(HR)-MFS. The surrogate threshold effect on OS was an HR(MFS) of 0.81. Conclusions: MFS remained a valid surrogate for OS in a more contemporary era, where patients had greater access to docetaxel and other systemic therapies for mCRPC. This supports the use of MFS as the primary outcome measure for ongoing adjuvant trials in localized PCa.
Keywords: metastasis-free survival;overall survival;prostate cancer;surrogate outcome
Document URI: http://hdl.handle.net/1942/46298
ISSN: 0923-7534
e-ISSN: 1569-8041
DOI: 10.1016/j.annonc.2023.11.017
ISI #: 001197990900001
Rights: 2023 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.
Category: A1
Type: Journal Contribution
Appears in Collections:Research publications

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