(UroToday.com) The treatment landscape in advanced prostate cancer has rapidly evolved. Docetaxel was the first agent to demonstrate a survival benefit in metastatic castration resistant prostate cancer (mCRPC) and has subsequently demonstrated benefit in metastatic castration-sensitive disease. However, the optimal use of docetaxel is not clear and it may be underutilized. Thus, biomarkers and prediction models assessing efficacy and toxicity of docetaxel may help optimize treatment selection.
In a moderated poster presentation at the American Urologic Association Annual Meeting, Dr. Cirulli and colleagues presented the results of their work examining risk stratification in this cohort.
To do so, the authors utilized the Project Data Sphere to access patient data from the control arms of three frontline mCRPC trials: ASCENT2, VENICE, and MAINSAIL. In each trial, treatment in the control arm consisted of docetaxel 75mg/m2 every 21 days + prednisone 5mg twice/day. They assessed the primary outcome of toxicity-related docetaxel discontinuation (TRDD). Reasons for docetaxel discontinuation were recorded and extensive demographic and clinical data were considered in a competing risks regression (CRR) to develop a model to predict TRDD. Cumulative incidence (CI) of TRDD was estimated after accounting for the occurrence of competing events (death or progression). This model was used to build a risk calculator to predict TRDD, the output of which was used in a classification and regression tree (CART) to identify 3 risk groups. Overall survival (OS) for the pooled cohort and for each risk group was assessed via the Kaplan-Meier (KM) method.
Among the three included trials, a total of 1568 patients were included. Over a median follow-up of 12.1 months, the median OS was 21 months.
Analysis using competing risks regression demonstrated significant associations with age, ECOG performance status, AST, bilirubin, use of analgesics, and presence of diabetes and chronic kidney disease. These were used in the predictive model and risk calculator.
The pooled cumulative incidence of TRDD was 19% after accounting for competing events (death, 474 patients and progression, 59 patients) within 12 months of starting treatment. The CART analysis identified three risk groups: low (model-derived TRDD risk ≤24%), intermediate (25-64%), and high (≥65%) risk group. In each risk group, the probability of TRDD during treatment was 14%, 58%, and 79%, and median OS was 24 months, 20 months, and 13 months, respectively (p<0.001).
Dr. Cirulli concluded that, among patients with mCRPC, this model can help clinicians balancing the toxicity and efficacy of docetaxel. The three risk categories identified correlate with overall survival and may help inform shared decision-making.
Presented by: Giuseppe Cirulli, MD, Urology Resident, San Raeffaele Hospital, MilanWritten by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2021 American Urological Association, (AUA) Annual Meeting, Fri, Sep 10, 2021 – Mon, Sep 13, 2021.