Cancer de la prostate résistant à la castration métastatique : utilisation des nouveaux traitements dans un contexte réel au Québec

Introduction: Since 2004, docetaxel-based chemotherapy has been the cornerstone of the management of metastatic castration-resistant prostate cancer (mCRPC). The therapeutic arsenal expanded in 2011 to involve several alternative drugs such as abiraterone and enzalutamide for use in docetaxel-refractory patients and then in docetaxel-naïve ones (since 2013). This study aimed to describe docetaxel, abiraterone (and enzalutamide) use and its associated factors in Quebec. It also aimed to describe bone-targeted therapy (denosumab and zoledronic acid) utilization and its associated factors in mCRPC patients. Methods: A retrospective cohort study was conducted in two of the main McGill University hospitals. Hospital-based cancer registries were used to identify patients treated for prostate cancer in medical oncology departments between January 1, 2010 and June 30, 2014. Then patients with mCRPC were selected. Patients’ medical charts were reviewed and mCRPC clinical data and treatments were extracted until May 10, 2016. The cohort was divided into two groups according to mCRPC diagnosis period. The cutoff date chosen was February 1, 2012 as it corresponded to the public reimbursement of abiraterone (and denosumab) in Quebec. Descriptive statistics were used to describe docetaxel, abiraterone, enzalutamide, and bone-targeted therapy (denosumab and zoledronic acid) utilization. The Kaplan-Meier method and log-rank test were used to estimate time to receive a first prescription for docetaxel and bone-targeted therapy since mCRPC diagnosis. Cox regression was used to identify predictive factors of docetaxel, abiraterone (or enzalutamide), and bone-targeted therapy use. Results: In our cohort, 308 patients with mCRPC were selected with 162 patients (53%) diagnosed with mCRPC before February 1, 2012 (pre-2012 group) and 146 (47%) diagnosed with mCRPC after February 1, 2012 (post-2012 group). The median age at mCRPC was 74.0 years old. In the pre-2012 group, patients received following treatments: docetaxel 82%, abiraterone 53%, and abiraterone or enzalutamide 54% versus 53%, 74% and 86%, respectively, in the post-2012 group. Factors associated with docetaxel use were having metastases (bone and lymph nodes, and visceral) at CRPC diagnosis, referral to an oncologist before mCRPC development, being younger than 80 at mCRPC diagnosis, having symptoms at mCRPC diagnosis and being diagnosed with mCRPC before 2012. Factors associated with abiraterone (or enzalutamide) use were having metastases (bone, lymph nodes, and visceral) at CRPC diagnosis, referral to an oncologist before mCRPC development, being older than 80 at mCRPC diagnosis, having cardiac or chronic comorbidites at mCRPC diagnosis and being diagnosed with mCRPC after 2012. The median time to have a prescription for docetaxel was delayed by six months in patients diagnosed after 2012 comparatively to those diagnosed before 2012 (p=0.0001). Among patients with bone metastases, 82% had at least one prescription for a bone-targeted therapy (denosumab or zoledronic acid). Factors associated with bone-targeted therapy use were having bone metastases at CRPC diagnosis, being diagnosed with mCRPC after 2012 and having symptoms at mCRPC diagnosis. Conclusion: The introduction of abiraterone (and enzalutamide) reduced overall docetaxel utilization and delayed time to its initiation. Metastases extent, age, moment of diagnosis with mCRPC, and referral to an oncologist before mCRPC development were the predictive factors either docetaxel, abiraterone or enzalutamide utilization. Patients with mCRPC benefit from bone-targeted therapy (denosumab or zoledronic acid) for bone metastases.

Keyphrases: Abiraterone, Docetaxel, Enzalutamide, Metastatic castration-resistant prostate cancer, Bone-targeted therapy, Real-world study, Drug utilization