Phase III SYNERGY trial: Docetaxel +/- custirsen and overall survival in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and poor prognosis.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 5009-5009 ◽  
Author(s):  
Kim N. Chi ◽  
Celestia S. Higano ◽  
Brent A. Blumenstein ◽  
James Andrew Reeves ◽  
Susan Feyerabend ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Poor Prognosis ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

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.

Association between radiographic response and overall survival in men with metastatic castration-resistant prostate cancer receiving chemotherapy.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 118-118
Author(s):  
G. Sonpavde ◽  
G. R. Pond ◽  
W. R. Berry ◽  
R. De Wit ◽  
M. A. Eisenberger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Objective Assessment ◽  
Objective Response ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Kaplan Meier

118 Background: In men with metastatic castration resistant prostate cancer (CRPC),the association of measurable tumor responses with overall survival (OS) is unknown. We retrospectively evaluated the TAX327 phase III trial to study this relationship. Methods: Eligible patients for this analysis included those with WHO-defined measurable metastatic disease randomized to receive either docetaxel or mitoxantrone. OS was estimated using the Kaplan-Meier method and the prognostic relationship of WHO-defined radiologic response with OS was performed using Cox proportional hazards regression. Landmark analyses evaluated survival from baseline and 2, 3, 4 and 6 months after baseline. Results: Four hundred and twelve patients enrolled on the TAX327 trial had measurable tumors. Thirty-seven patients exhibited a complete or partial objective response (CR/PR, 9.0%), 116 had stable disease (SD, 28.2%), 99 had progressive disease (PD,24%) and 160 (38.8%) did not have a post-baseline objective assessment. Partial responders demonstrated longer median OS (29.0 months) than patients with SD (22.1 months), or those with PD (10.8 months) or those who were not assessed (12.7 months). These results remained after landmark analysis. We found a significant association between ≥30% PSA declines and radiologic response, with ≥30% PSA declines occurring in all patients with CR/PR, 79.8% of patients with SD and 34.4% with PD. Radiologic response remained a significant but modest post-treatment prognostic factor for OS after adjusting for treatment, pain-response and ≥30% PSA-decline (p=0.009). Conclusions: In men with metastatic CRPC and measurable disease receiving chemotherapy, objective tumor response was prognostic for OS, and appears to complement PSA assessment. [Table: see text]

scholarly journals A predictive model of overall survival in patients with metastatic castration-resistant prostate cancer

F1000Research ◽  
2019 ◽  
Vol 5 ◽  
pp. 2674
Author(s):  
Mehrad Mahmoudian ◽  
Fatemeh Seyednasrollah ◽  
Liisa Koivu ◽  
Outi Hirvonen ◽  
Sirkku Jyrkkiö ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Clinical Features ◽  
Clinical Information ◽  
Phase Iii ◽  
Prognostic Models ◽  
Castration Resistant Prostate Cancer ◽  
Phase Iii Clinical Trials ◽  
Castration Resistant ◽  
Improved Performance

Metastatic castration resistant prostate cancer (mCRPC) is one of the most common cancers with a poor prognosis. To improve prognostic models of mCRPC, the Dialogue for Reverse Engineering Assessments and Methods (DREAM) Consortium organized a crowdsourced competition known as the Prostate Cancer DREAM Challenge. In the competition, data from four phase III clinical trials were utilized. A total of 1600 patients’ clinical information across three of the trials was used to generate prognostic models, whereas one of the datasets (313 patients) was held out for blinded validation. The previously introduced prognostic model of overall survival of chemotherapy-naive mCRPC patients treated with docetaxel or prednisone (so called Halabi model) was used as a performance baseline. This paper presents the model developed by the team TYTDreamChallenge and its improved version to predict the prognosis of mCRPC patients within the first 30 months after starting the treatment based on available clinical features of each patient. In particular, by replacing our original larger set of eleven features with a smaller more carefully selected set of only five features the prediction performance on the independent validation cohort increased up to 5.4 percent. While the original TYTDreamChallenge model (iAUC=0.748) performed similarly as the performance-baseline model developed by Halabi et al. (iAUC=0.743), the improved post-challenge model (iAUC=0.779) showed markedly improved performance by using only PSA, ALP, AST, HB, and LESIONS as features. This highlights the importance of the selection of the clinical features when developing the predictive models.

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.

PROfound: A randomized Phase III trial evaluating olaparib in patients with metastatic castration-resistant prostate cancer and a deleterious homologous recombination DNA repair aberration.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS5091-TPS5091 ◽  
Author(s):  
Johann S. De Bono ◽  
Maha Hussain ◽  
Antoine Thiery-Vuillemin ◽  
Joaquin Mateo ◽  
A. Oliver Sartor ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Homologous Recombination ◽  
Radiographic Progression ◽  
Response Rate ◽  
Objective Response ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

TPS5091 Background: The median overall survival for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) is short. Available agents may offer limited therapeutic benefit, but no molecularly stratified treatment has yet been approved for this heterogeneous disease. A sizable percentage of pts with mCRPC has loss of function aberrations in genes involved in homologous recombination repair (HRR) in tumor tissue, such as BRCA1/2 and ATM. These aberrations can confer sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition. A Phase II study indicated that the oral PARP inhibitor olaparib (Lynparza) had antitumor activity in 33% of mCRPC pts who had progressed after new hormonal agent (NHA) treatment and chemotherapy, with a strikingly higher composite response rate in pts with a deleterious HRR gene aberration (HRRa) (88%; 14/16) vs pts without a HRRa (6%; 2/33) (Mateo et al.2015). The PROfound study evaluates olaparib efficacy and safety versus physician’s choice of either abiraterone acetate or enzalutamide, in pts with mCRPC and a HRRa (NCT02987543). Methods: To be eligible for this multinational, open-label, Phase III study, mCRPC pts must have progressed on prior NHA treatment and have a tumor HRRa in one of 15 genes, as confirmed by an HRR Assay (Foundation Medicine, Inc.). Cohort A (n = 240 approx) includes pts with mutations in BRCA1, BRCA2 or ATM, while pts with a mutation in 12 other HRR genes will be assigned to Cohort B (n = 100 approx). Pts will be randomized (2:1) to olaparib tablets (300 mg orally bid) or physician’s choice of either enzalutamide (160 mg orally od) or abiraterone acetate (1000 mg orally od with 5 mg bid prednisone) and treatment continued until radiographic progression (as assessed by blinded independent central review) or lack of treatment tolerability. The primary endpoint of radiographic progression-free survival (rPFS) will be assessed in Cohort A using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria. Key secondary efficacy endpoints include confirmed objective response rate, time to pain progression, overall survival (all Cohort A) and rPFS (both cohorts combined). Clinical trial information: NCT02987543.

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.

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