Ahmad Halwani

Abstract A055: Racial disparities in metastatic castrate-resistant prostate cancer (mCRPC): Evidence from the Veterans Health Administration (VHA)

Purpose: Describe patients, disease characteristics, and treatment patterns of a nationwide cohort of black men with mCRPC in the largest nationwide integrated health care system in the United States: the VHA. Background: Black men have an increased incidence of prostate cancer, are diagnosed at an earlier age than white men with similar demographic and disease characteristics, and experience worse clinical outcomes (1–4). This study examines disease characteristics and treatment practices among black men with mCRPC over a 10-year period for the first 2 lines of therapy in the VHA. Methods: Patient information was obtained from the Veterans Affairs (VA) Clinical Cancer Registry (VACCR) and the VA Corporate Data Warehouse (CDW) to identify patients who were diagnosed with prostate cancer at the VA and later developed mCRPC, defined as: (1) radiologic evidence of metastasis obtained from radiology reports using a natural language processing algorithm (5); (2) evidence of rising prostate-specific antigen (PSA), i.e., 2 consecutive increases in the PSA concentration over a baseline value, retrieved from the CDW/ VA Informatics and Computing Infrastructure (VINCI) Lab Chemistry package using the Clinical Lab Information Retrieval (CLIR) (6); (3) evidence of ongoing androgen deprivation consisting of a serum testosterone level of ≤ 50 ng/dL (≤ 2.0 nmol/L), retrieved from the CDW/ VINCI Lab Chemistry package using the CLIR pipeline, whereby the values were extracted based on the LOINC code and/or lab test name. Treatments of mCRPC were identified by review of the NCCN Prostate Cancer Guidelines V2.2017. Therapies were extracted from CDW pharmacy dispensation records (docetaxel, abiraterone, enzalutamide, etc.). Race/ethnicity data were obtained from VACCR. Classification of race/ethnicity using VA data was previously validated by Kressin et al (7). Charlson Comorbidity Index (CCI) was calculated using Quan comorbidity mapping (8). Results: 120,374 patients were diagnosed with prostate cancer and treated in the VA from 2006 to 2016; of these, 3,637 developed mCRPC, of whom 2,429 (67%) were white, 1,066 (29%) were black, and 142 (4%) were reported as other. Compared with white men, at diagnosis black men were younger (66 vs. 69 years) and had a higher PSA (92.25 ng/mL vs. 41 ng/mL). Disease characteristics at diagnosis were comparable: Gleason 2-6 (1% vs. 1%), 7 (19% vs. 22%), 8-10 (66% vs. 63%); Stages II (28% vs. 32%), III (5% vs. 4%), IV (61% vs. 60%). Treatment did not differ significantly: radiation (26% vs. 26%), prostatectomy (6% vs. 4%), surgical orchiectomy (2% vs. 1%), castration by agonists (85% vs. 86%), castration by agonists/androgen deprivation (34% vs. 33%). Cytotoxic agent docetaxel was the primary first-line therapy for both black and white men (28% and 27%). More white men received first-line abiraterone acetate (AA; 22%) compared with black men (19%), although more black men than white men received second-line AA (17% vs. 14%). Similar treatment patterns between black and white men were observed when the results were further stratified by time period (2006-2010 vs. 2011-2016). Conclusions: This is the first study of a large, nationwide, contemporary cohort of black men with mCRPC treated in an integrated equal-access health care system, the VHA. Consistent with prior reports, black men with mCRPC were younger and had higher PSA values, although treatment patterns between the 2 groups were similar. References: 1. DeSantis CE, et al. CA Cancer J Clin 2016;66:290-308. 2. Robbins AS, et al. Am J Epidemiol 2007;166:71-8. 3. Moul JW, et al. J Urol 1996;155:1667-73. 4. Tsodikov A, et al. Cancer 2017;123:2312-2319. 5. Chapman WW, et al. J Biomed Inform 2001;34:301-10. 6. Halwani A, et al. VAAHO 2016 [abstract 41]. 7. Kressin NR, et al. Am J Public Health 2003;93:1734-9. 8. Quan H, et al. Med Care 2005;43:1130-9. Citation Format: Ahmad Halwani, Kelli M. Rasmussen, Vikas Patil, Zachary Burningham, Sujata Narayanan, Shih-Wen Lin, Susheela Carroll, Ling-I Hsu, Julie N. Graff, Robert Dreicer, Sumati Gupta, Clarke Low, Brian C. Sauer. Racial disparities in metastatic castrate-resistant prostate cancer (mCRPC): Evidence from the Veterans Health Administration (VHA) [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A055.

Pralatrexate Monitoring Using a Commercially Available Methotrexate Assay to Avoid Potential Drug Interactions

Pralatrexate (PDX) is a folate antagonist structurally similar to methotrexate (MTX). Unlike MTX, it is currently not known whether PDX exhibits delayed clearance and heightened toxicity in the setting of fluid overload. A specific serum assay for PDX is not commercially available. To our knowledge, we report the first case using an MTX serum assay as a surrogate for PDX concentrations to avoid a potential drug‐drug interaction with pralatrexate. We describe a 76‐year‐old man with refractory cutaneous T‐cell lymphoma who began therapy with weekly PDX 15 mg/m2 intravenous infusions on days 1, 8, and 15 of a 28‐day cycle. He subsequently developed mucositis, a moderate right‐sided pleural effusion, and peripheral edema over the next 5 weeks. Aggressive diuresis with furosemide was initiated, which was then withheld the day before his next PDX dose to avoid a potential drug‐drug interaction between PDX and furosemide. His baseline MTX/PDX concentration (measured prior to administration of the cycle 2, week 2 PDX dose) was less than 0.20 μmol/L (i.e., undetectable). After PDX administration, his 1‐hour peak MTX/PDX concentration increased to 0.58 μmol/L. Aggressive diuresis was withheld until his MTX/PDX concentration was undetectable, 43.5 hours later. PDX is more potent than MTX and displays similar pharmacokinetic properties. PDX concentrations using the serum MTX assay reflect lower values than those reported from PDX‐specific assays in clinical studies. Because PDX is approved by the U.S. Food and Drug Administration for the treatment of uncommon malignancies, it is unlikely that a specific assay will be commercially developed. We propose that the MTX serum assay has merit for use in determining when to reinstate possible interacting drug therapies such as loop diuretics.