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
Authors Cheng S, Arciero V, Goldberg H, Tajzler C, Manganaro A, Kozlowski N, Rowbottom L, McDonald R, Chow R, Vasisht G, Shaji S, Wong ECL, Petrovic M, Zhang L, Phillips C, Zalewski P, Kapoor A, Fleshner NE, Chow E, Emmenegger U
Received 22 April 2019
Accepted for publication 25 September 2019
Published 31 October 2019 Volume 2019:11 Pages 9307—9319
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Amy Norman
Peer reviewer comments 3
Editor who approved publication: Dr Kenan Onel
Sierra Cheng,1 Vanessa Arciero,1 Hanan Goldberg,2 Camilla Tajzler,3 Aileen Manganaro,4 Natascha Kozlowski,4 Leigha Rowbottom,1 Rachel McDonald,1 Ronald Chow,1 Gaurav Vasisht,3 Sharon Shaji,3 Emily Chu Lee Wong,3 Michele Petrovic,2 Liying Zhang,1 Cameron Phillips,1 Pawel Zalewski,4 Anil Kapoor,3 Neil E Fleshner,2 Edward Chow,1 Urban Emmenegger1
1Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada; 2Princess Margaret Cancer Centre, Toronto, Ontario, Canada; 3Juravinski Cancer Centre, Hamilton, Ontario, Canada; 4Durham Regional Cancer Centre, Oshawa, Ontario, Canada
Correspondence: Urban Emmenegger
Sunnybrook Odette Cancer Centre, 2075 Bayview Avenue, Toronto, Ontario M4N3M5, Canada
Tel +1-416-480 4928
Fax +1-416-480 6002
Introduction: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
Keywords: radium 223, metastatic prostate cancer, real-world, predictive markers of outcome
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