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Surrogate endpoints for overall survival for patients with metastatic hormone-sensitive prostate cancer in the CHAARTED trial

Prostate Cancer and Prostatic Diseases volume 23, pages 638–645 (2020)Cite this article

Subjects

Abstract

Background

Metastasis-free survival has been shown to be a robust surrogate for overall survival (OS) in men with nonmetastatic prostate cancer (PC). However, this surrogate only holds true for a select subset of patients, and leaves those trials analyzing metastatic disease at a disadvantage. We aimed to identify the best surrogate for predicting OS in patients with metastatic hormone-sensitive PC.

Methods

We analyzed data from the Chemohormonal Therapy versus Androgen Ablation Randomized Trial for Extensive Disease trial in which patients were randomly assigned to receive either androgen deprivation therapy (ADT) or ADT plus docetaxel. PSA response, progression and development of castration-resistant PC (CRPC) within 6 and 12 months were investigated as potential OS surrogates, in accordance with the Prentice Criteria. The proportion the of treatment effect (PTE) was calculated for each surrogate and used to identify the best one.

Results

Data from 790 patients were considered: 393 (49.7%) men received ADT alone, while 397 (50.3%) received combination therapy. Four intermediate clinical endpoints met the criteria for surrogacy: progression within 6 months (HR: 5.70; 95%CI: 4.26, 7.64; p < 0.001) and 12 months (HR: 7.09; 95%CI: 5.16, 9.76; p < 0.001) as well as development of CRPC within 6 (HR: 5.11; 95%CI: 3.81, 6.85; p < 0.001) and 12 months (HR: 6.24; 95%CI: 4.58, 8.51; p < 0.001). The PTE for the four surrogates were 88%, 52%, 80%, and 46%, respectively. The 2-year OS rates for patients who progressed within 6 months of randomization were 42 versus 89% for the patient population that did not progress that quickly.

Conclusions

Progression within 6 months following combination therapy emerged as the best surrogate for OS.

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Fig. 1: Kaplan–Meier survivor functions stratified according to each intermediate clinical endpoint demonstrating overall survival.
Fig. 2

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Acknowledgements

This paper was prepared using data from Datasets NCT00309985-D3 from the National Clinical Trials Network (NCTN) Data Archive of the National Cancer Institute’s (NCI’s) NCTN. Data were originally collected from clinical trial NCT number NCT00309985, Chemohormonal Therapy versus Androgen Ablation Randomized Trial for Extensive Disease (CHAARTED). All analyses and conclusions in this paper are the sole responsibility of the authors and do not necessarily reflect the opinions or views of the clinical trial investigators, the NCTN, or the NCI. Data were accessed through http://www.projectdatasphere.org/, which is maintained by Project Data Sphere, LLC (PDS). Neither PDS nor the owner(s) of any information from the Web site have contributed to, approved, or are in any way responsible for the contents of this publication.

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Authors and Affiliations

  1. Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Alberto Martini & John Pfail

  2. Department of Urology, Vita-Salute San Raffaele University, Milan, Italy

    Alberto Martini & Francesco Montorsi

  3. Department of Medicine, Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Matthew D. Galsky & William K. Oh

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  1. Alberto Martini
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Corresponding author

Correspondence to Alberto Martini.

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Conflict of interest

MDG has served as consultant for BioMotiv, Janssen, Merk, Dendreon, GlaxoSmithKline, Lilly, Astellas, Genetech, BMS, Novartis, Pfizer, EMD Serono, AZ, Seattle Genetics, Incyte, Aileron Therapeutics, Dracen, Inovio Pharmaceuticals, NuMab, has received research funding from Janssen, Merk, Dendreon, Novartis, BMS, AZ, Genentech/Roche, and owns stock of Rapt Therapeutics, outside the submitted work. WKO has served as consultant for Sema4, Sanofi, Astellas, Bayer, Janssen, outside the submitted work.

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Martini, A., Pfail, J., Montorsi, F. et al. Surrogate endpoints for overall survival for patients with metastatic hormone-sensitive prostate cancer in the CHAARTED trial. Prostate Cancer Prostatic Dis 23, 638–645 (2020). https://doi.org/10.1038/s41391-020-0231-5

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