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A DREAM Challenge to Build Prediction Models for Short-Term Discontinuation of Docetaxel in Metastatic Castration-Resistant Prostate Cancer.
- Source :
-
JCO clinical cancer informatics [JCO Clin Cancer Inform] 2017 Nov; Vol. 1, pp. 1-15. - Publication Year :
- 2017
-
Abstract
- Purpose: Docetaxel has a demonstrated survival benefit for patients with metastatic castration-resistant prostate cancer (mCRPC); however, 10% to 20% of patients discontinue docetaxel prematurely because of toxicity-induced adverse events, and the management of risk factors for toxicity remains a challenge.<br />Patients and Methods: The comparator arms of four phase III clinical trials in first-line mCRPC were collected, annotated, and compiled, with a total of 2,070 patients. Early discontinuation was defined as treatment stoppage within 3 months as a result of adverse treatment effects; 10% of patients discontinued treatment. We designed an open-data, crowd-sourced DREAM Challenge for developing models with which to predict early discontinuation of docetaxel treatment. Clinical features for all four trials and outcomes for three of the four trials were made publicly available, with the outcomes of the fourth trial held back for unbiased model evaluation. Challenge participants from around the world trained models and submitted their predictions. Area under the precision-recall curve was the primary metric used for performance assessment.<br />Results: In total, 34 separate teams submitted predictions. Seven models with statistically similar area under precision-recall curves (Bayes factor ≤ 3) outperformed all other models. A postchallenge analysis of risk prediction using these seven models revealed three patient subgroups: high risk, low risk, or discordant risk. Early discontinuation events were two times higher in the high-risk subgroup compared with the low-risk subgroup. Simulation studies demonstrated that use of patient discontinuation prediction models could reduce patient enrollment in clinical trials without the loss of statistical power.<br />Conclusion: This work represents a successful collaboration between 34 international teams that leveraged open clinical trial data. Our results demonstrate that routinely collected clinical features can be used to identify patients with mCRPC who are likely to discontinue treatment because of adverse events and establishes a robust benchmark with implications for clinical trial design.
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Antineoplastic Agents administration & dosage
Antineoplastic Combined Chemotherapy Protocols adverse effects
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Clinical Trials as Topic
Docetaxel administration & dosage
Humans
Male
Meta-Analysis as Topic
Middle Aged
Prednisone
Prognosis
Prostatic Neoplasms, Castration-Resistant mortality
Time Factors
Treatment Outcome
Young Adult
Antineoplastic Agents therapeutic use
Docetaxel therapeutic use
Models, Theoretical
Prostatic Neoplasms, Castration-Resistant drug therapy
Prostatic Neoplasms, Castration-Resistant pathology
Subjects
Details
- Language :
- English
- ISSN :
- 2473-4276
- Volume :
- 1
- Database :
- MEDLINE
- Journal :
- JCO clinical cancer informatics
- Publication Type :
- Academic Journal
- Accession number :
- 30657384
- Full Text :
- https://doi.org/10.1200/CCI.17.00018