Sundhar Ramalingam1, Michael S Humeniuk2, Rachel Hu2, Julia Rasmussen2, Patrick Healy3, Yuan Wu3, Michael R Harrison4, Andrew J Armstrong4, Daniel J George4, Tian Zhang4. 1. Duke University Medical Center, Durham, NC; Department of Biostatistics and Bioinformatics, Duke University, Durham, NC. Electronic address: sundhar.ramalingam@dm.duke.edu. 2. Duke University Medical Center, Durham, NC. 3. Duke University Medical Center, Durham, NC; Department of Biostatistics and Bioinformatics, Duke University, Durham, NC. 4. Duke University Medical Center, Durham, NC; Duke Cancer Institute, Durham, NC.
Abstract
PURPOSE: Evidence suggests differences in androgen receptor AR signaling between black (B) and white (W) patients with prostate cancer, but pivotal trials of abiraterone acetate (AA) for patients with metastatic castration-resistant prostate cancer (mCRPC) enrolled few black patients, a population with a higher mortality from prostate cancer. Our primary objective was to determine differences in response to AA between B and W patients. METHODS: We performed a retrospective case-control study of B vs. W patients treated with AA between May 1, 2008 and June 16, 2015 at Duke University Medical Center. Patients were identified (W control patients were matched 2:1 to B patients stratified based on previous docetaxel exposure) through pharmacy records and were eligible if treated with AA for metastatic castration-resistant prostate cancer. Patients with previous enzalutamide use were excluded. The primary objective was to compare the rate of≥90% prostate-specific antigen (PSA) decline from baseline between B vs. W patients. Secondary outcomes included comparing time on therapy, time to PSA progression, and overall survival among groups. RESULTS: Baseline characteristics among patients (n = 45 B, n = 90 W) were identified; these included Karnofsky performance status, PSA, Gleason score, alkaline phosphatase, albumin, hemoglobin, lactate dehydrogenase, opiate use for pain, and metastatic sites. Baseline characteristics among groups were similar except for median hemoglobin (B = 11.4g/dl, W = 12.3g/dl). The proportion of B patients achieving a≥90% PSA level decline was 37.8% vs. 28.9% for W patients (P = 0.296). Statistically significant differences were found in the proportion of patients achieving a≥50% PSA level decline (B = 68.9%, W = 48.9% [P = 0.028]) and≥30% PSA level decline (B = 77.8%, W = 54.4% [P = 0.008]). Rates of primary abiraterone-refractory disease (PSA increase as best response) trended higher in W (31.1%) than in B (15.6%) patients (P = 0.052). Median treatment duration (B = 9.4 mo, W = 8.3 mo) did not differ (Wilcoxon P = 0.444). Median overall survival (B = 27.3 mo [95% CI: 13.9, not estimable], W = 24.8 mo [95% CI: 19, 31.6] [P = 0.669]) and median time to PSA progression (B = 11.0 mo [95% CI: 4.3, 18.0], W = 9.4 mo [95% CI: 6.2, 13.0] [P = 0.917]) did not differ. CONCLUSIONS: Black patients may have a higher PSA response to AA than white patients. An ongoing prospective clinical study (NCT01940276) is evaluating outcomes between black and white patients treated with AA.
PURPOSE: Evidence suggests differences in androgen receptor AR signaling between black (B) and white (W) patients with prostate cancer, but pivotal trials of abiraterone acetate (AA) for patients with metastatic castration-resistant prostate cancer (mCRPC) enrolled few black patients, a population with a higher mortality from prostate cancer. Our primary objective was to determine differences in response to AA between B and W patients. METHODS: We performed a retrospective case-control study of B vs. W patients treated with AA between May 1, 2008 and June 16, 2015 at Duke University Medical Center. Patients were identified (W control patients were matched 2:1 to B patients stratified based on previous docetaxel exposure) through pharmacy records and were eligible if treated with AA for metastatic castration-resistant prostate cancer. Patients with previous enzalutamide use were excluded. The primary objective was to compare the rate of≥90% prostate-specific antigen (PSA) decline from baseline between B vs. W patients. Secondary outcomes included comparing time on therapy, time to PSA progression, and overall survival among groups. RESULTS: Baseline characteristics among patients (n = 45 B, n = 90 W) were identified; these included Karnofsky performance status, PSA, Gleason score, alkaline phosphatase, albumin, hemoglobin, lactate dehydrogenase, opiate use for pain, and metastatic sites. Baseline characteristics among groups were similar except for median hemoglobin (B = 11.4g/dl, W = 12.3g/dl). The proportion of B patients achieving a≥90% PSA level decline was 37.8% vs. 28.9% for W patients (P = 0.296). Statistically significant differences were found in the proportion of patients achieving a≥50% PSA level decline (B = 68.9%, W = 48.9% [P = 0.028]) and≥30% PSA level decline (B = 77.8%, W = 54.4% [P = 0.008]). Rates of primary abiraterone-refractory disease (PSA increase as best response) trended higher in W (31.1%) than in B (15.6%) patients (P = 0.052). Median treatment duration (B = 9.4 mo, W = 8.3 mo) did not differ (Wilcoxon P = 0.444). Median overall survival (B = 27.3 mo [95% CI: 13.9, not estimable], W = 24.8 mo [95% CI: 19, 31.6] [P = 0.669]) and median time to PSA progression (B = 11.0 mo [95% CI: 4.3, 18.0], W = 9.4 mo [95% CI: 6.2, 13.0] [P = 0.917]) did not differ. CONCLUSIONS: Black patients may have a higher PSA response to AA than whitepatients. An ongoing prospective clinical study (NCT01940276) is evaluating outcomes between black and whitepatients treated with AA.
Authors: Daniel J George; Lorelei A Mucci; Ilkania M Chowdhury-Paulino; Caroline Ericsson; Randy Vince; Daniel E Spratt Journal: Prostate Cancer Prostatic Dis Date: 2021-09-02 Impact factor: 5.455
Authors: Daniel J George; Susan Halabi; Elisabeth I Heath; A Oliver Sartor; Guru P Sonpavde; Devika Das; Rhonda L Bitting; William Berry; Patrick Healy; Monika Anand; Carol Winters; Colleen Riggan; Julie Kephart; Rhonda Wilder; Kellie Shobe; Julia Rasmussen; Matthew I Milowsky; Mark T Fleming; James Bearden; Michael Goodman; Tian Zhang; Michael R Harrison; Megan McNamara; Dadong Zhang; Bonnie L LaCroix; Rick A Kittles; Brendon M Patierno; Alexander B Sibley; Steven R Patierno; Kouros Owzar; Terry Hyslop; Jennifer A Freedman; Andrew J Armstrong Journal: Cancer Date: 2021-05-05 Impact factor: 6.921
Authors: Giuseppe Fallara; Ingela Franck Lissbrant; Johan Styrke; Francesco Montorsi; Hans Garmo; Pär Stattin Journal: PLoS One Date: 2020-12-28 Impact factor: 3.240
Authors: Taraswi Mitra Ghosh; Jason White; Joshua Davis; Suman Mazumder; Teeratas Kansom; Elena Skarupa; Grafton S Barnett; Gary A Piazza; R Curtis Bird; Amit K Mitra; Clayton Yates; Brian S Cummings; Robert D Arnold Journal: Front Pharmacol Date: 2021-12-06 Impact factor: 5.810
Authors: Joaquin Mateo; Rana McKay; Wassim Abida; Rahul Aggarwal; Joshi Alumkal; Ajjai Alva; Felix Feng; Xin Gao; Julie Graff; Maha Hussain; Fatima Karzai; Bruce Montgomery; William Oh; Vaibhav Patel; Dana Rathkopf; Matthew Rettig; Nikolaus Schultz; Matthew Smith; David Solit; Cora Sternberg; Eliezer Van Allen; David VanderWeele; Jake Vinson; Howard R Soule; Arul Chinnaiyan; Eric Small; Jonathan W Simons; William Dahut; Andrea K Miyahira; Himisha Beltran Journal: Nat Cancer Date: 2020-11-17