Practice patterns for metastatic castration-resistant prostate cancer (mCRPC) have evolved over the last decade due to introduction of agents such as abiraterone and enzalutamide. This study examines mCRPC treatment practices over a 10-year period (which includes the time periods before and after the introduction of novel oral anti-androgens) for the first 3 lines of therapy in the largest nationwide integrated health system in the United States, the Veterans Health Administration.
By linking patient information from the Veterans Affairs (VA) Clinical Cancer Registry to clinical notes, laboratory, procedure and imaging data from the VA Corporate Data Warehouse (CDW), we identified patients who were diagnosed with prostate cancer at the VA and ultimately developed mCRPC, defined as radiological evidence of metastasis and evidence of rising PSA levels concomitant with surgical (bilateral orchiectomy) or medical castrate testosterone levels (≤ 50 ng/dL within the last 3 months or ongoing treatment with androgen deprivation). Therapies used to treat mCRPC were extracted from CDW pharmacy dispensation records (docetaxel, abiraterone, enzalutamide, cabazitaxel, and others).
From 2006 to 2015, 120,374 patients were diagnosed with prostate cancer, of whom 3,637 developed mCRPC. Median age at initial prostate diagnosis was 68 years (range, 41-94), average BMI was 26.5 (range, 9-59), average CCI score was 1.5 (range, 0-12) and average PSA was 45.5 ng/mL. Practices for the first 3 lines of treatment from 2006 to 2010 and 2011 to 2016 are summarized in Table 1. Patients diagnosed with mCRPC between 2006 and 2010 were more likely to receive cytotoxic therapy than patients diagnosed between 2011 and 2016 (37% vs 22%). Compared with the cohort diagnosed between 2006 and 2010, the later cohort was more likely to receive treatment (44% vs 62%) and was also more likely to receive > 1 line of therapy (20% vs 37%). For patients diagnosed between 2011 and 2016, the most common therapies were as follows: 1L, abiraterone (29%); 2L, abiraterone (15%) and enzalutamide (14%); and 3L, enzalutamide (8%).Table:
|ENTIRE COHORTa (2006-2016) N = 3,637||mCRPC Diagnosis (2006-2010) N = 1,118||mCRPC Diagnosis (2011-2016) N = 2,519|
|1L, % pts 2L, % pts 3L, % pts||DOC 27%, AA 22%, ENZ 6% AA 13%, ENZ 10%, DOC 4% ENZ 6%, DOC 4%, AA 3%||DOC 37%, AA 4%, ENZ 1% AA 7%, MIT 5%, CAB 3% AA 3%, ENZ 2%, DOC 2%||AA 29%, DOC 22%, ENZ 9% AA 15%, ENZ 14%, DOC 6% ENZ 8%, DOC 5%, AA 3%|
|No treatment, % pts||1L 43%, 2L 68%, 3L 86%||1L 56%, 2L 80%, 3L 90%||1L 38%, 2L 63%, 3L 81%|
|Top 3 most common treatment sequences from 1L to 2L (% of pts)||DOC-AA (11%) AA-ENZ (8%) AA-DOC (4%)||DOC-AA (7%) DOC-MIT (5%) DOC-CAB (3%)||DOC-AA (12%) AA-ENZ (11%) AA-DOC (5%)|
AA, abiraterone acetate; CAB, cabazitaxel; DOC, docetaxel; ENZ, enzalutamide; MIT, mitoxantrone a
Our study is the first to describe adoption of non-chemotherapeutic treatments in a nationwide cohort of patients with mCRPC treated in the largest integrated healthcare system in the United States. Further research will focus on understanding clinical outcomes associated with this shift in practice patterns.
Clinical trial identification
Legal entity responsible for the study
Ahmad Halwani, MD
A. Halwani: Research funding: Kyowa Hikko Kirin, BMS, Seattle Genetics, Roche/Genentech, Genentech, Takeda, Pharmacyclics, Amgen, Abbvie, Immune Design, Miragen, Seattle Genetics. S. Narayanan: Stock ownership and employee of Roche/Genentech Inc. S-W. Lin: Stock ownership and employee of Roche/Genentech Inc. S. Carroll: Stock ownership and employee of by Genentech Inc. L-I. Hsu: Stock owner and employee of Genentech Inc. J. Graff: Honorarium from Astellas, research funding from Sanofi, Merck, Bristol Myers Squibb, Astellas, Janssen, travel funds from Sanofi, Merck, and Clovis. R. Dreicer: Consulting relationships with: Orion, Medivation, Astellas, Asana, Genentech, Roche, AstraZeneca, Exelexis, Eisai, Bristol Myers Squibb, Sanofi-Genzyme, EMD Serono. S. Gupta: Spouse: Stock ownership in Salarius Pharmaceuticals. B.C. Sauer: Research funding from Genentech Inc. and Amgen. All other authors have declared no conflicts of interest.