scholarly journals Overall Survival of Black and White Men With Metastatic Castration-Resistant Prostate Cancer Treated With Docetaxel

2019 ◽  
Vol 37 (5) ◽  
pp. 403-410 ◽  
Author(s):  
Susan Halabi ◽  
Sandipan Dutta ◽  
Catherine M. Tangen ◽  
Mark Rosenthal ◽  
Daniel P. Petrylak ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Black Men ◽  
Performance Status ◽  
Specific Antigen ◽  
White Men ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Black And White ◽  
Castration Resistant

Purpose Several studies have reported that among patients with localized prostate cancer, black men have a shorter overall survival (OS) time than white men, but few data exist for men with advanced prostate cancer. The primary goal of this analysis was to compare the OS in black and white men with metastatic castration-resistant prostate cancer (mCRPC) who were treated in phase III clinical trials with docetaxel plus prednisone (DP) or a DP-containing regimen. Methods Individual participant data from 8,820 men with mCRPC randomly assigned in nine phase III trials to DP or a DP-containing regimen were combined. Race was based on self-report. The primary end point was OS. The Cox proportional hazards regression model was used to assess the prognostic importance of race (black v white) adjusted for established risk factors common across the trials (age, prostate-specific antigen, performance status, alkaline phosphatase, hemoglobin, and sites of metastases). Results Of 8,820 men, 7,528 (85%) were white, 500 (6%) were black, 424 (5%) were Asian, and 368 (4%) were of unknown race. Black men were younger and had worse performance status, higher testosterone and prostate-specific antigen, and lower hemoglobin than white men. Despite these differences, the median OS was 21.0 months (95% CI, 19.4 to 22.5 months) versus 21.2 months (95% CI, 20.8 to 21.7 months) in black and white men, respectively. The pooled multivariable hazard ratio of 0.81 (95% CI, 0.72 to 0.91) demonstrates that overall, black men have a statistically significant decreased risk of death compared with white men ( P < .001). Conclusion When adjusted for known prognostic factors, we observed a statistically significant increased OS in black versus white men with mCRPC who were enrolled in these clinical trials. The mechanism for these differences is not known.

Apalutamide, darolutamide and enzalutamide in nonmetastatic castration-resistant prostate cancer: a meta-analysis

2021 ◽  
Author(s):  
Mathieu Roumiguié ◽  
Xavier Paoletti ◽  
Yann Neuzillet ◽  
Romain Mathieu ◽  
Sebastien Vincendeau ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Meta Analysis ◽  
Specific Antigen ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Phase Iii Clinical Trials ◽  
Castration Resistant ◽  
Related Quality ◽  
Health Related

Aim: Comparison of the efficacy/safety/health-related quality of life of apalutamide, enzalutamide and darolutamide in Phase III clinical trials involving patients with nonmetastatic castration-resistant prostate cancer was performed. Materials & methods: Relevant studies were identified by searching PubMed as well as conference abstracts reporting updated overall survival. Three pivotal trials were identified, SPARTAN (apalutamide), PROSPER (enzalutamide) and ARAMIS (darolutamide), and form the basis of this analysis. Results: All three drugs significantly prolonged metastasis-free survival, prostate-specific antigen response and overall survival versus placebo, and were generally well tolerated. Conclusion: Drug selection will likely be influenced by tolerability/safety and other factors, such as the propensity for drug–drug interactions and the presence of comorbidities, that affect the risk–benefit balance in individual patients.

Overall survival between African-American (AA) and Caucasian (C) men with metastatic castration-resistant prostate cancer (mCRPC).

2018 ◽  
Vol 36 (18_suppl) ◽  
pp. LBA5005-LBA5005 ◽  
Author(s):  
Susan Halabi ◽  
Sandipan Dutta ◽  
Catherine M. Tangen ◽  
Mark Rosenthal ◽  
Daniel Peter Petrylak ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
Overall Survival ◽  
Alkaline Phosphatase ◽  
African American ◽  
Lymph Nodes ◽  
Performance Status ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

LBA5005 Background: Reports have suggested that African-American (AA) men with metastatic castration-resistant prostate cancer (mCRPC) have shorter overall survival (OS) than Caucasian (C) men. Prior reports have been limited by small sample size. The primary goal of this analysis was to compare OS in AA men to Caucasian men treated with docetaxel/prednisone or a docetaxel/prednisone containing regimen. Methods: Individual patient data from 8,871 mCRPC men randomized on nine phase III trials to docetaxel/prednisone (DP) or a DP containing regimen were combined. Race used in the analysis was based on self-report. The primary endpoint is OS, defined as the time between randomization and death or date of last follow-up if patients were alive. The proportional hazards model was used to assess the prognostic importance of race (AA vs. C) adjusting for established risk factors that were common across the trials (age, PSA, performance status, alkaline phosphatase, hemoglobin, and sites of metastases). Results: Of 8,871 patients, 7,528 (85%) were C, 500 (6%) were AA, 424 were Asian (5%) and 419 (4%) had race unspecified. The last two groups were deleted from the analysis leaving 8,452 pts. Median age was 69 years and 94% had performance status 0-1. Median hemoglobin, PSA and alkaline phosphatase were 12.9 g/dL, 86 ng/mL and 139 U/L, respectively. Pattern of metastatic spread were: 72% bone disease with or without lymph nodes, 9% lung disease, 9% liver disease and 7% lymph nodes only. Median OS were 21.0 (95% CI = 19.4-22.5) vs. 21.2 months (95% CI = 20.8-21.7) in AAs and C, respectively. In multivariable analysis adjusting for established risk factors, the pooled hazard ratio (HR) for AAs vs. Caucasians was 0.81 (95% CI = 0.72-0.92, p-value = 0.001) in all patients. Similar results were observed in 4,172 of patients who were treated with DP. Conclusions: We observed a statistically significant increased OS in AA vs. C men with mCRPC who were eligible to be enrolled on these clinical trials. Further understanding the biological variation by race in men with mCRPC treated with DP is warranted.

scholarly journals Survival by race in men with chemotherapy-naive enzalutamide- or abiraterone-treated metastatic castration-resistant prostate cancer

2021 ◽  
Author(s):  
Daniel J. George ◽  
Krishnan Ramaswamy ◽  
Ahong Huang ◽  
David Russell ◽  
Jack Mardekian ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Black Men ◽  
White Men ◽  
Subsequent Treatment ◽  
Veterans Health ◽  
Health Administration ◽  
Castration Resistant Prostate Cancer ◽  
Cox Models ◽  
Black And White ◽  
Castration Resistant

Abstract Background Black men are more likely to be diagnosed with aggressive prostate cancer (PC) and die from PC than white men. However, black men with metastatic castration-resistant PC (mCRPC) had longer overall survival (OS) than white men when treated with certain agents in clinical trials. We analyzed claims data from the Veterans Health Administration (VHA) database to evaluate OS in black and white men treated with enzalutamide or abiraterone (novel hormonal therapy [NHT]) for chemotherapy-naïve mCRPC. Methods Patients with mCRPC aged ≥18 years were identified in the VHA database by diagnosis codes, evidence of surgical/medical castration, and a prescription claim for enzalutamide or abiraterone after castration from April 2014–March 2017. Cox models assessed associations between race and OS. Unadjusted and multivariable analyses were performed on the entire population and subsets based on the type of therapy received (if any) after NHT. Results In total, 2910 patients were identified (787 black, mean 71.7 years; 2123 white, mean 74.0 years). Median follow-up was 19.0 and 18.7 months in blacks and whites, respectively. Black men had better survival versus white men: hazard ratios (95% CIs) were 0.89 (0.790–0.996; P = 0.044) and 0.67 (0.592–0.758; P < 0.0001) in the unadjusted and multivariable models, respectively. Statistically significantly longer OS was seen in black versus white men regardless of subsequent treatment, including no subsequent treatment. Conclusions In the VHA, black men with chemotherapy-naïve mCRPC initiating NHT may have better outcomes than similarly treated white men.

scholarly journals Overall Survival Analysis of a Phase II Randomized Controlled Trial of a Poxviral-Based PSA-Targeted Immunotherapy in Metastatic Castration-Resistant Prostate Cancer

2010 ◽  
Vol 28 (7) ◽  
pp. 1099-1105 ◽  
Author(s):  
Philip W. Kantoff ◽  
Thomas J. Schuetz ◽  
Brent A. Blumenstein ◽  
L. Michael Glode ◽  
David L. Bilhartz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Phase Ii ◽  
Viral Vectors ◽  
Controlled Trial ◽  
Specific Antigen ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Randomized Controlled ◽  
Castration Resistant

PurposeTherapeutic prostate-specific antigen (PSA) –targeted poxviral vaccines for prostate cancer have been well tolerated. PROSTVAC-VF treatment was evaluated for safety and for prolongation of progression-free survival (PFS) and overall survival (OS) in a randomized, controlled, and blinded phase II study.Patients and MethodsIn total, 125 patients were randomly assigned in a multicenter trial of vaccination series. Eligible patients had minimally symptomatic castration-resistant metastatic prostate cancer (mCRPC). PROSTVAC-VF comprises two recombinant viral vectors, each encoding transgenes for PSA, and three immune costimulatory molecules (B7.1, ICAM-1, and LFA-3). Vaccinia-based vector was used for priming followed by six planned fowlpox-based vector boosts. Patients were allocated (2:1) to PROSTVAC-VF plus granulocyte-macrophage colony-stimulating factor or to control empty vectors plus saline injections.ResultsEighty-two patients received PROSTVAC-VF and 40 received control vectors. Patient characteristics were similar in both groups. The primary end point was PFS, which was similar in the two groups (P = .6). However, at 3 years post study, PROSTVAC-VF patients had a better OS with 25 (30%) of 82 alive versus 7 (17%) of 40 controls, longer median survival by 8.5 months (25.1 v 16.6 months for controls), an estimated hazard ratio of 0.56 (95% CI, 0.37 to 0.85), and stratified log-rank P = .0061.ConclusionPROSTVAC-VF immunotherapy was well tolerated and associated with a 44% reduction in the death rate and an 8.5-month improvement in median OS in men with mCRPC. These provocative data provide preliminary evidence of clinically meaningful benefit but need to be confirmed in a larger phase III study.

scholarly journals Circulating Tumor Cell Number as a Response Measure of Prolonged Survival for Metastatic Castration-Resistant Prostate Cancer: A Comparison With Prostate-Specific Antigen Across Five Randomized Phase III Clinical Trials

2018 ◽  
Vol 36 (6) ◽  
pp. 572-580 ◽  
Author(s):  
Glenn Heller ◽  
Robert McCormack ◽  
Thian Kheoh ◽  
Arturo Molina ◽  
Matthew R. Smith ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Specific Antigen ◽  
Circulating Tumor Cell ◽  
Phase Iii ◽  
Response Measure ◽  
Castration Resistant Prostate Cancer ◽  
End Points ◽  
End Point ◽  
Castration Resistant

Purpose Measures of response that are clinically meaningful and occur early are an unmet need in metastatic castration-resistant prostate cancer clinical research and practice. We explored, using individual patient data, week 13 circulating tumor cell (CTC) and prostate-specific antigen (PSA) response end points in five prospective randomized phase III trials that enrolled a total of 6,081 patients—COU-AA-301, AFFIRM, ELM-PC-5, ELM-PC-4, and COMET-1— ClinicalTrials.Gov identifiers: NCT00638690, NCT00974311, NCT01193257, NCT01193244, and NCT01605227, respectively. Methods Eight response end points were explored. CTC nonzero at baseline and 0 at 13 weeks (CTC0); CTC conversion (≥ 5 CTCs at baseline, ≤ 4 at 13 weeks—the US Food and Drug Administration cleared response measure); a 30%, 50%, and 70% decrease in CTC count; and a 30%, 50%, and 70% decrease in PSA level. Patients missing week-13 values were considered nonresponders. The discriminatory strength of each end point with respect to overall survival in each trial was assessed using the weighted c-index. Results Of the eight response end points, CTC0 and CTC conversion had the highest weighted c-indices, with smaller standard deviations. For CTC0, the mean (standard deviation) was 0.81 (0.04); for CTC conversion, 0.79 (0.03); for 30% decrease in CTC count, 0.72 (0.06); for 50% decrease in CTC count, 0.72 (0.06); for 70% decrease in CTC count, 0.73 (0.05); for 30% decrease in PSA level, 0.71 (0.03); for 50% decrease in PSA level, 0.72 (0.06); and for 70% decrease in PSA level, 0.74 (0.05). Seventy-five percent of eligible patients could be evaluated with the CTC0 end point, compared with 51% with the CTC conversion end point. Conclusion The CTC0 and CTC conversion end points had the highest discriminatory power for overall survival. Both are robust and meaningful response end points for early-phase metastatic castration-resistant prostate cancer clinical trials. CTC0 is applicable to a significantly higher percentage of patients than CTC conversion.

Cabazitaxel Versus Docetaxel As First-Line Therapy for Patients With Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase III Trial—FIRSTANA

2017 ◽  
Vol 35 (28) ◽  
pp. 3189-3197 ◽  
Author(s):  
Stéphane Oudard ◽  
Karim Fizazi ◽  
Lisa Sengeløv ◽  
Gedske Daugaard ◽  
Fred Saad ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Purpose In patients with metastatic castration-resistant prostate cancer (mCRPC), overall survival (OS) is significantly improved with cabazitaxel versus mitoxantrone after prior docetaxel treatment. FIRSTANA ( ClinicalTrials.gov identifier: NCT01308567) assessed whether cabazitaxel 20 mg/m2 (C20) or 25 mg/m2 (C25) is superior to docetaxel 75 mg/m2 (D75) in terms of OS in patients with chemotherapy-naïve mCRPC. Patients and Methods Patients with mCRPC and Eastern Cooperative Oncology Group performance status of 0 to 2 were randomly assigned 1:1:1 to receive C20, C25, or D75 intravenously every 3 weeks plus daily prednisone. The primary end point was OS. Secondary end points included safety; progression-free survival (PFS); tumor, prostate-specific antigen, and pain response; pharmacokinetics; and health-related quality of life. Results Between May 2011 and April 2013, 1,168 patients were randomly assigned. Baseline characteristics were similar across cohorts. Median OS was 24.5 months with C20, 25.2 months with C25, and 24.3 months with D75. Hazard ratio for C20 versus D75 was 1.01 (95% CI, 0.85 to 1.20; P = .997), and hazard ratio for C25 versus D75 was 0.97 (95% CI, 0.82 to 1.16; P = .757). Median PFS was 4.4 months with C20, 5.1 months with C25, and 5.3 months with D75, with no significant differences between treatment arms. Radiographic tumor responses were numerically higher for C25 (41.6%) versus D75 (30.9%; nominal P = .037, without multiplicity test adjustment). Rates of grade 3 or 4 treatment-emergent adverse events were 41.2%, 60.1%, and 46.0% for C20, C25, and D75, respectively. Febrile neutropenia, diarrhea, and hematuria were more frequent with C25; peripheral neuropathy, peripheral edema, alopecia, and nail disorders were more frequent with D75. Conclusion C20 and C25 did not demonstrate superiority for OS versus D75 in patients with chemotherapy-naïve mCRPC. Tumor response was numerically higher with C25 versus D75; pain PFS was numerically improved with D75 versus C25. Cabazitaxel and docetaxel demonstrated different toxicity profiles, with overall less toxicity with C20.

scholarly journals Randomized, Double-Blind, Placebo-Controlled Phase III Trial Comparing Docetaxel and Prednisone With or Without Bevacizumab in Men With Metastatic Castration-Resistant Prostate Cancer: CALGB 90401

2012 ◽  
Vol 30 (13) ◽  
pp. 1534-1540 ◽  
Author(s):  
William Kevin Kelly ◽  
Susan Halabi ◽  
Michael Carducci ◽  
Daniel George ◽  
John F. Mahoney ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Phase Iii ◽  
Controlled Study ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Purpose A randomized, placebo-controlled study based on preclinical and clinical data that supports the potential role of vascular endothelial growth factor in prostate cancer was performed to evaluate the addition of bevacizumab to standard docetaxel and prednisone therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). Patients and Methods Patients with chemotherapy-naive progressive mCRPC with Eastern Cooperative Oncology Group performance status ≤ 2 and adequate bone marrow, hepatic, and renal function were randomly assigned to receive docetaxel 75 mg/m2 intravenously (IV) over 1 hour for 21 days plus prednisone 5 mg orally twice per day (DP) with either bevacizumab 15 mg/kg IV every 3 weeks (DP + B) or placebo. The primary end point was overall survival (OS), and secondary end points were progression-free survival (PFS), 50% decline in prostate-specific antigen, objective response (OR), and toxicity. Results In total, 1,050 patients were randomly assigned. The median OS for patients given DP + B was 22.6 months compared with 21.5 months for patients treated with DP (hazard ratio, 0.91; 95% CI, 0.78 to 1.05; stratified log-rank P = .181). The median PFS time was superior in the DP + B arm (9.9 v 7.5 months, stratified log-rank P < .001) as was the proportion of patients with OR (49.4% v 35.5%; P = .0013). Grade 3 or greater treatment-related toxicity was more common with DP + B (75.4% v 56.2%; P ≤ .001), as was the number of treatment-related deaths (4.0% v 1.2%; P = .005). Conclusion Despite an improvement in PFS and OR, the addition of bevacizumab to docetaxel and prednisone did not improve OS in men with mCRPC and was associated with greater toxicity.

scholarly journals Comparative Survival of Asian and White Metastatic Castration-Resistant Prostate Cancer Men Treated With Docetaxel

2020 ◽  
Vol 4 (2) ◽  
Author(s):  
Susan Halabi ◽  
Sandipan Dutta ◽  
Catherine M Tangen ◽  
Mark Rosenthal ◽  
Daniel P Petrylak ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
White Men ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Risk Of Death ◽  
Castration Resistant ◽  
Increased Risk ◽  
Asian Men ◽  
Few Data

Abstract There are few data regarding disparities in overall survival (OS) between Asian and white men with metastatic castration-resistant prostate cancer (mCRPC). We compared OS of Asian and white mCRPC men treated in phase III clinical trials with docetaxel and prednisone (DP) or a DP-containing regimen. Individual participant data from 8820 men with mCRPC randomly assigned on nine phase III trials to receive DP or a DP-containing regimen were combined. Men enrolled in these trials had a diagnosis of prostate adenocarcinoma. The median overall survival was 18.8 months (95% confidence interval [CI] = 17.4 to 22.1 months) and 21.2 months (95% CI = 20.8 to 21.7 months) for Asian and white men, respectively. The pooled hazard ratio for death for Asian men compared with white men, adjusted for baseline prognostic factors, was 0.95 (95% CI = 0.84 to 1.09), indicating that Asian men were not at increased risk of death. This large analysis showed that Asian men did not have shorter OS duration than white men treated with docetaxel.

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