Population-Based Analysis Of The Use Of Radium-223 For Bone-Metastatic Castration-Resistant Prostate Cancer In Ontario, And Of Factors Associated With Treatment Completion And Outcome.

Radium-223 (Ra223) prolongs the survival and improves the quality of life of men with metastatic, castration-resistant prostate cancer (mCRPC) to bones. However, compared to other mCRPC therapies, using Ra223 comes with its unique challenges. Hence, we aimed to identify Ra223 utilization patterns under real-world conditions, as well as factors predicting treatment completion and outcome. In this retrospective chart analysis, 198 mCRPC patients were identified that had received Ra223 outside of clinical trials or access programs from January 2015 to October 2016 at four cancer centres in Ontario. The main outcomes studied were Ra223 completion rate, reasons for early treatment discontinuation, overall survival, and survival differences in patients completing Ra223 therapy versus patients receiving <6 cycles of Ra223. In addition, patient and disease characteristics were analysed to identify predictors of treatment completion and survival. In this cohort of patients mostly pretreated with abiraterone and/or enzalutamide (92.4%), almost half of which had also received docetaxel (48.5%), the Ra223 completion rate was 46.5%, and the actuarial median survival was 13.3 months. The main reason for early Ra223 discontinuation was disease progression, and Ra223 non-completion was associated with poorer outcome (median survival 8.1 months [6.0-12.2] versus 18.7 months [15.3-22.3] in men completing Ra223, p<0.0001). Lymph node metastases and a high baseline prostate-specific antigen (PSA) were independent predictors of early treatment discontinuation. Multivariable Cox proportional hazards models revealed early Ra223 discontinuation, baseline anemia, high PSA, prior skeletal-related events, visceral metastases, and being referred to another centre for Ra223 therapy as predictors of worse outcome. Despite a lower completion rate than observed under clinical trial conditions, the real-world results achieved with Ra223 are encouraging. If prospectively validated, predictive patient and disease characteristics identified in our cohort might become instrumental to identify mCRPC patients likely to complete and to most benefit from Ra223 therapy.

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© 2019 Cheng et al.

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Pawel Zalewski: Consulting or Advisory Role: Bayer Inc. Canada. Anil Kapoor: Consulting or Advisory Role: Bayer Inc. Canada; reports grants, personal fees from Bayer Oncology, during the conduct of the study. Neil E Fleshner: Consulting or Advisory Role: Bayer Inc. Canada; reports personal fees from Abbvie, personal fees from Amgen, grants, personal fees from Bayer, grants, personal fees from Ferring, grants, personal fees from Janssen, grants, personal fees from Sanofi, personal fees from Hybridyne Health, grants, personal fees from Astellas, grants from Bavarian Nordic, grants from Medivation, grants from Nucleix, grants from Progenics, grants from Spectracure AB, outside the submitted work. Research Support: Bayer Inc. Canada. Edward Chow: Consulting or Advisory Role: Bayer Inc. Canada. Urban Emmenegger: Consulting or Advisory Role, Research support: Bayer Inc. Canada; reports grants from Bayer, during the conduct of the study. Consulting or Advisory Role: Amgen Inc. Canada. Consulting or Advisory Role: Astellas Inc. Canada. Research Support: AstraZeneca Inc. Canada. Research Support: Endocyte Inc. (Novartis Inc.). Research Support: Exelixis Inc. Consulting or Advisory Role: Ferring Inc. Canada. Consulting or Advisory Role, Research Support: Janssen Inc. Canada. Research support: Merck Inc. Canada. Research support: Roche-Genentech Inc. Canada. Consulting or Advisory Role: Sanofi Genzyme Inc. Canada. The aforementioned authors report no other conflicts of interest in this work. The remaining authors report no conflicts of interest in this work.