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Predicting toxicity-related docetaxel discontinuation and overall survival in metastatic castration-resistant prostate cancer: a pooled analysis of open phase 3 clinical trial data

Prostate Cancer and Prostatic Diseases volume 24, pages 743–749 (2021)Cite this article

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Abstract

Background

Docetaxel is widely used in metastatic castration-resistant prostate cancer (mCRPC), however its optimal use remains unclear in the current treatment landscape. Biomarkers to predict Docetaxel toxicity may help optimize treatment selection. We aimed to create a predictive model for toxicity-related Docetaxel discontinuation (TRDD).

Methods

Through Project Data Sphere, we accessed individual patient data from the control arms of three frontline mCRPC trials: ASCENT2, VENICE, and MAINSAIL. The inclusion criteria for these trials were all similar and included patients with chemotherapy-naïve mCRPC. The primary outcome was occurrence of TRDD. A competing risks regression (CRR) was used to predict TRDD, after accounting for the occurrence of competing events (death or progression). The output of the model was used as the dependent variable on a classification and regression tree (CART) to identify risk groups for TRDD.

Results

Overall, 1568 patients were considered. Pooled CI of TRDD was 19% after accounting for competing events (death: 474; progression: 59) within 12 months of starting treatment. To build a risk calculator we relied on a CRR that ultimately included age, ECOG performance status, AST, bilirubin, use of analgesics, and presence of diabetes and chronic kidney disease. The CART analysis identified three risk groups that were named: low (model-derived TRDD risk ≤24%), intermediate (25–64%), and high (≥65%) risk group. In each risk group, 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).

Conclusions

Treatment selection in mCRPC remains a challenge. Our model can help clinicians balance Docetaxel toxicity and efficacy. The three risk categories that we identified correlated with OS and this is particularly useful for an optimal shared decision-making process.

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Author notes

  1. These authors contributed equally: Alberto Martini, Anish B. Parikh

Authors and Affiliations

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

    Alberto Martini & John P. Sfakianos

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

    Alberto Martini & Francesco Montorsi

  3. Genitourinary Oncology Section, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center - James Cancer Hospital, Columbus, OH, USA

    Anish B. Parikh

  4. Division of Hematology/Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Anish B. Parikh, Matthew D. Galsky, William K. Oh & Che-Kai Tsao

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  1. Alberto Martini
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Correspondence to Alberto Martini.

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Martini, A., Parikh, A.B., Sfakianos, J.P. et al. Predicting toxicity-related docetaxel discontinuation and overall survival in metastatic castration-resistant prostate cancer: a pooled analysis of open phase 3 clinical trial data. Prostate Cancer Prostatic Dis 24, 743–749 (2021). https://doi.org/10.1038/s41391-021-00326-3

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