A DREAM challenge to build pbkp_rediction models for short-term discontinuation of docetaxel in metastatic castration- resistant prostate cancer

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. Patients and Methods The comparator arms of four phase III clinical trials in first-linem CRPC 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 adversetreatment effects; 10% of patients discontinued treatment. We designed an open-data, crowd-sourced DREAM Challenge for developing models with which to pbkp_redict 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 pbkp_redictions. Area under the precision-recall curve was the primary metric used for performance assessment. Results In total, 34 separate teams submitted pbkp_redictions. Seven models with statistically similar area under precision-recall curves (Bayes factor≤3) outperformed all other models. Apostchallenge analysis of risk pbkp_rediction 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 pbkp_rediction models could reduce patient enrollment in clinical trials without the loss of statistical power. Conclusion This work represents a successful collaboration between 34international 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.

Año de publicación:

2017

Keywords:

Fuente:

scopus