CUA 2017: Population-Based Analysis of Treatment Toxicity Among Men with Castration-Resistant Prostate Cancer (mCRPC)

Toronto, Ontario (UroToday.com) At the GU oncology poster session at the 2017 CUA annual meeting, Dr. Christopher Wallis and colleagues from Toronto presented their population-based findings analyzing treatment toxicity among men with metastatic castration-resistant prostate cancer (mCRPC). Indeed, the toxicity and effectiveness of contemporary mCRPC treatments have not been assessed at a population level.

The purpose of this study was to examine rates of hospitalizations and emergency room (ER) visits and survival among men with mCRPC treated with abiraterone, enzalutamide, docetaxel, or cabazitaxel.

For this phase 4, population-based, retrospective study in Ontario, Canada (2003-2015), 2,439 men age ≥65 years of age with mCRPC receiving treatment with abiraterone, enzalutamide, docetaxel, or cabazitaxel were included. Co-primary outcomes were toxicity (hospitalizations and ER visits) and overall survival from the date of first mCRPC prescription. Hazard ratios (HRs) were calculated using multivariable Cox proportional hazards models with time-varying exposures. Docetaxel was associated with a significantly increased risk of any-cause (HR 1.3; 95%CI 1.2‒1.4) and treatment-related (HR 1.5; 95%CI 1.3‒1.7) toxicity, while cabazitaxel was associated with a significant risk of treatment-related (HR 5.9; 95%CI 1.9‒18.9), but not any-cause (HR 2.4; 95%CI 0.6‒9.6) toxicity. Importantly, abiraterone and enzalutamide exposure were not associated with any-cause (p=0.2 and 0.5, respectively) or treatment-related (p=0.5 and 0.6, respectively) toxicities. The authors did note effect modification with an elevated risk of toxicity during abiraterone treatment among patients who had prior receipt of chemotherapy. Patients starting mCRPC treatment following the introduction of oral therapies had improved overall survival compared with those starting prior to their introduction (adjusted HR 0.70; 95%CI 0.64‒0.77). The strength of this study is the novel use of population-level data over a long period of enrolment. 

The authors concluded that among patients with mCRPC, treatment with docetaxel or cabazitaxel was associated with an increased risk of hospitalizations and ER visits. Further, there was no association with abiraterone or enzalutamide exposure, although the use of abiraterone following chemotherapy was associated with an increased risk of toxicity. These results likely lend credence to utilizing chemotherapy earlier in the disease course when the likelihood of tolerability is higher, rather than later in the palliative setting of mCRPC when morbidity and mortality are greater.

Presented By: Christopher JD. Wallis, MD, PhD, University of Toronto, Toronto, ON

Co-Authors: Raj Satkunasivam, Refik Saskin, Symron Bansal, Girish S. Kulkarni, Urban Emmenegger, Robert K. Nam

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre  Twitter: @zklaassen_md at the  72nd Canadian Urological Association Annual Meeting - June 24 - 27, 2017 - Toronto, Ontario, Canada
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