scholarly journals Identification of subgroups of metastatic castrate-resistant prostate cancer (mCRPC) patients treated with abiraterone plus prednisone at low- vs. high-risk of radiographic progression: An analysis of COU-AA-302

2018 ◽  
Vol 13 (6) ◽  
Author(s):  
Lisa J. Martin ◽  
Shabbir M.H. Alibhai ◽  
Maria Komisarenko ◽  
Narhari Timilshina ◽  
Antonio Finelli
Keyword(s):  
Prostate Cancer ◽  
Radiographic Progression ◽  
Proportional Hazards ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Limited Resource ◽  
Abiraterone Acetate ◽  
Cox Proportional Hazards ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

Introduction: Radiographic imaging is used to monitor disease progression for men with metastatic castrate-resistant prostate cancer (mCRPC). The optimal frequency of imaging, a costly and limited resource, is not known. Our objective was to identify predictors of radiographic progression to inform the frequency of imaging for men with mCRPC. Methods: We accessed data for men with chemotherapy-naive mCRPC in the abiraterone acetate plus prednisone (AA-P) group of a randomized trial (COU-AA-302) (n=546). We used Cox proportional hazards modelling to identify predictors of time to progression. We divided patients into groups based on the most important predictors and estimated the probability of radiographic progression-free survival (RPFS) at six and 12 months. Results: Baseline disease and change in prostate-specific antigen (PSA) at eight weeks were the strongest determinants of RPFS. The probability of RPFS for men with bone-only disease and a ≥50% fall in PSA was 93% (95% confidence interval [CI] 87–96) at six months and 80% (95% CI 72–86) at 12 months. In contrast, the probability of RPFS for men with bone and soft tissue metastasis and <50% fall in PSA was 55% (95% CI 41–67) at six months and 34% (95% CI 22–47) at 12 months. These findings should be externally validated. Conclusions: Patients with chemotherapy-naive mCRPC treated with first-line AA-P can be divided into groups with significantly different risks of radiographic progression based on a few clinically available variables, suggesting that imaging schedules could be individualized.

scholarly journals Progression-Free Survival as a Predictor of Overall Survival in Men With Castrate-Resistant Prostate Cancer

2009 ◽  
Vol 27 (17) ◽  
pp. 2766-2771 ◽  
Author(s):  
Susan Halabi ◽  
Nicholas J. Vogelzang ◽  
San-San Ou ◽  
Kouros Owzar ◽  
Laura Archer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Free Survival ◽  
Castrate Resistant Prostate Cancer ◽  
Biochemical Progression ◽  
Castrate Resistant

Purpose To explore whether progression-free survival (PFS) or biochemical PFS can be used as a predictor of overall survival (OS) and to investigate the dependence between PFS and OS in men with castrate-resistant prostate cancer. Patients and Methods Data from nine Cancer and Leukemia Group B trials that enrolled 1,296 men from 1991 to 2004 were pooled. Men were eligible if they had prostate cancer that had progressed during androgen deprivation therapy and did not receive prior treatment with chemotherapy, immunotherapy, or other nonhormonal therapy. Landmark analyses of PFS at 3 and 6 months from randomization/registration were performed to minimize lead time bias. The proportional hazards model was used to assess the significance effect of PFS rate at 3 and at 6 months in predicting OS. In addition, biochemical progression using the definitions of Prostate-Specific Antigen Working Group (PSAW) Criteria PSAWG1 and PSAWG2 were analyzed as time-dependent covariates in predicting OS. Results The median survival time among men who experienced progression at 3 months was 9.2 months (95% CI, 8.0 to 10.0 months) compared with 17.8 months in men who did not experience progression at 3 months (95% CI, 16.2 to 20.4 months; P < .0001). Compared with men who did not progress at 3 and at 6 months, the adjusted hazard ratios for death were 2.0 (95% CI, 1.7 to 2.4; P < .001) and 1.9 (95% CI, 1.6 to 2.4; P < .001) for men who experienced progression at 3 and 6 months, respectively. In addition, biochemical progression at 3 months predicted OS. The association between PFS and OS was 0.30 (95% confidence limits = 0.26, 0.32). Conclusion PFS at 3 and 6 months and biochemical progression at 3 months predict OS. These observations require prospective validation.

Radiographic progression-free survival as a surrogate endpoint of overall survival in men with metastatic castrate-resistant prostate cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5057-5057
Author(s):  
Susan Halabi ◽  
Akash Roy ◽  
Qian Yang ◽  
Wanling Xie ◽  
William Kevin Kelly ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiographic Progression ◽  
Progression Free Survival ◽  
Surrogate Endpoint ◽  
Phase Iii ◽  
Random Assignment ◽  
Moderate Correlation ◽  
Free Survival ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

5057 Background: Radiographic progression-free survival (rPFS) is commonly used as a co-primary endpoint in randomized clinical trials in men with metastatic castrate-resistant prostate cancer (mCRPC). However, rPFS has not been established as a valid surrogate endpoint of overall survival (OS) in men with mCRPC. Here, we hypothesized that rPFS is a reliable surrogate for OS in mCRPC. We also explored whether PFS is a valid surrogate endpoint of OS at the aggregate trial level. Methods: We performed a systematic search of the literature encompassing the period January 2004-December 2020 using PubMed and clinical trials.gov to identify completed phase III trials in mCRPC post-docetaxel. Eligible trials had to be randomized phase III therapeutic trials that reported OS, PFS or rPFS. OS was measured from the date of random assignment to date of death from any cause or date of last follow-up. rPFS was defined as the time from random assignment to date of disease progression on CT and/or Tc bone scan per trial definition or death from any cause, whichever occurred first. PFS included PSA progression as a component of the composite endpoint. Trial level surrogacy was evaluated by fitting linear regression on the treatment effect of rPFS (or PFS) and OS (in other words, the weighted linear regression of the log(hazard ratio) of OS on the log(hazard ratio) of rPFS). It was pre-specified that rPFS would be considered a valid surrogate for OS if R² was 0·7 or higher. Results: We identified 33 in men with mCRPC post docetaxel approval. We assessed the association between PFS and OS in 29,456 patients from 30 trials. Overall, a moderate correlation was observed at the trial level between OS and PFS ( R2 = 0.46, 95 %CI = 0.20-0.68) in these trials. In 18 trials with 16,818 mCRPC patients where rPFS was considered as a key endpoint, a moderate correlation between the treatment effects on rPFS and OS was observed at the trial level ( R2= 0.65, 95% CI = 0.23-0.87). Conclusions: This meta-analysis demonstrates moderate correlation between treatment effects of rPFS and OS in patients with mCRPC. However, rPFS did not meet the pre-specified surrogacy threshold of 0.7. Clinical trial information: several.

scholarly journals Effects of Abiraterone Acetate on Androgen Signaling in Castrate-Resistant Prostate Cancer in Bone

2012 ◽  
Vol 30 (6) ◽  
pp. 637-643 ◽  
Author(s):  
Eleni Efstathiou ◽  
Mark Titus ◽  
Dimitra Tsavachidou ◽  
Vassiliki Tzelepi ◽  
Sijin Wen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Bone Marrow Aspirate ◽  
Specific Antigen ◽  
Abiraterone Acetate ◽  
Open Label ◽  
Clinical Observations ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Tumor Expression

Purpose Persistent androgen signaling is implicated in castrate-resistant prostate cancer (CRPC) progression. This study aimed to evaluate androgen signaling in bone marrow–infiltrating cancer and testosterone in blood and bone marrow and to correlate with clinical observations. Patients and Methods This was an open-label, observational study of 57 patients with bone-metastatic CRPC who underwent transiliac bone marrow biopsy between October 2007 and March 2010. Patients received oral abiraterone acetate (1 g) once daily and prednisone (5 mg) twice daily. Androgen receptor (AR) and CYP17 expression were assessed by immunohistochemistry, testosterone concentration by mass spectrometry, AR copy number by polymerase chain reaction, and TMPRSS2-ERG status by fluorescent in situ hybridization in available tissues. Results Median overall survival was 555 days (95% CI, 440 to 965+ days). Maximal prostate-specific antigen decline ≥ 50% occurred in 28 (50%) of 56 patients. Homogeneous, intense nuclear expression of AR, combined with ≥ 10% CYP17 tumor expression, was correlated with longer time to treatment discontinuation (> 4 months) in 25 patients with tumor-infiltrated bone marrow samples. Pretreatment CYP17 tumor expression ≥ 10% was correlated with increased bone marrow aspirate testosterone. Blood and bone marrow aspirate testosterone concentrations declined to less than picograms-per-milliliter levels and remained suppressed at progression. Conclusion The observed pretreatment androgen-signaling signature is consistent with persistent androgen signaling in CRPC bone metastases. This is the first evidence that abiraterone acetate achieves sustained suppression of testosterone in both blood and bone marrow aspirate to less than picograms-per-milliliter levels. Potential admixture of blood with bone marrow aspirate limits our ability to determine the origin of measured testosterone.

Comparison of survival of African-American (AA) patients (pts) in docetaxel (D)-based combination therapies in metastatic castrate-resistant prostate cancer (mCRPC).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 272-272
Author(s):  
Fatima Karzai ◽  
Ravi Amrit Madan ◽  
Yang-Min Ning ◽  
Marc Robert Theoret ◽  
Philip M. Arlen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Median Number ◽  
Incidence And Mortality ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Number Of Cycles ◽  
Ecog Ps

272 Background: AA pts experience greater prostate cancer (PC) incidence and mortality compared to Caucasian (C) pts but are underrepresented in clinical trials (CTs). Greater representation of AAs is required to explore differences in clinical benefit in advanced disease where recent data has reaffirmed the role of D. Methods: In a retrospective analysis, baseline characteristics, Gleason score (GS), ECOG PS, number of cycles (cys), maximum prostate-specific antigen (PSA) declines, radiographic responses, overall survival (OS) and progression-free survival (PFS) were captured in 2 recent D based CTs. Results: Of 136 pts, 28 (21%) self-identified as Black or AA. Median age of AA pts is 66 (50-78 yrs). Median GS is 8 (5-10). Median ECOG PS is 1 (0-2). 15 pts have bone and soft tissue disease; 13 pts have bone only disease. Median number of cys is 28.5 (1-63). Of 27 evaluable pts, 26 had PSA declines (-26 to -99%). Radiographic responses include 11 (39%) partial responses and 16 (57%) pts with stable disease. Median OS for AAs is 29.0 months (mos) (95% CI: 20.9-34.7 mos); median PFS is 21.5 mos (95% CI: 13.7-28.9 mos). Median OS for all non-AA pts is 24.8 mos (95% CI: 21.8-29.5 mos); median PFS is 16.1 mos (95% CI: 14.1-20.1 mos). The VEGF-634G > C SNP, associated with a more aggressive phenotype of PC, was evaluated in 54 pts. No evidence was found that genotype frequency varies between C and AA pts. Conclusions: In this analysis, AA pts did not have inferior OS (29 mos) or PFS (21.5 mos) outcomes compared to non-AA pts (24.8, 16.1 mos). Further analysis from larger studies is required to determine differential benefits of D for AA pts compared to non-AA pts. Clinical trial information: NCT00089609, NCT00942578.

Emerging Treatments for Castrate-Resistant Prostate Cancer

2011 ◽  
Vol 24 (4) ◽  
pp. 366-373
Author(s):  
Michell B. Redding ◽  
Minal Surati
Keyword(s):  
Prostate Cancer ◽  
Antitumor Agents ◽  
Specific Antigen ◽  
Abiraterone Acetate ◽  
Cytotoxic Agents ◽  
Emerging Treatments ◽  
Castrate Resistant Prostate Cancer ◽  
New Treatment ◽  
Castrate Resistant ◽  
Androgen Depletion

Castrate-resistant prostate cancer (CRPC) is a challenging aspect in the treatment of prostate cancer. Research has identified several pathways in the pathogenesis of CRPC. Several new agents targeting some of these pathways have shown promising data during clinical trials. In the area of androgen depletion, abiraterone acetate and MDV100 have been studied and have shown to decrease prostate-specific antigen (PSA) levels in phase I and II studies. Bevacizumab is a monoclonal antibody antiangiogenesis agent that targets vascular endothelial growth factor (VEGF) and has shown to decrease PSA levels in combination with other cytotoxic agents. Three agents, ixabepilone, patupilone, and sagopilone, in the class of epothilones (tubulin polymerizing antitumor agents), have shown moderate reductions in PSA levels and moderate adverse effects. The results of ongoing studies with these new treatment agents may offer viable alternatives to the traditional treatment of CRPC to decrease disease progression and improve overall survival.

scholarly journals Impact of comorbidity on the outcome in men with advanced prostate cancer treated with docetaxel

2015 ◽  
Vol 49 (4) ◽  
pp. 402-408 ◽  
Author(s):  
Andrej Zist ◽  
Eitan Amir ◽  
Alberto F. Ocana ◽  
Bostjan Seruga
Keyword(s):  
Prostate Cancer ◽  
Proportional Hazards ◽  
Hospital Admissions ◽  
Univariate Analysis ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Severe Comorbidity ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
The Impact

Abstract Background. Men with metastatic castrate-resistant prostate cancer (mCRPC) may not receive docetaxel in everyday clinical practice due to comorbidities. Here we explore the impact of comorbidity on outcome in men with mCRPC treated with docetaxel in a population-based outcome study. Methods. Men with mCRPC treated with docetaxel at the Institute of Oncology Ljubljana between 2005 and 2012 were eligible. Comorbidity was assessed by the age-adjusted Charlson comorbidity index (aa-CCI) and adult comorbidity evaluation (ACE-27) index. Hospital admissions due to the toxicity and deaths during treatment with docetaxel were used as a measure of tolerability. Association between comorbidity and overall survival (OS) was tested using the Cox proportional hazards analysis. Results. Two hundred and eight men were treated with docetaxel. No, mild, moderate and severe comorbidity was present in 2%, 32%, 53% and 13% using aa-CCI and in 27%, 35%, 29% and 8% when assessed by ACE-27. A substantial dose reduction of docetaxel occurred more often in men with moderate or severe comorbidity as compared to those with no or mild comorbidity. At all comorbidity levels about one-third of men required hospitalization or died during treatment with docetaxel. In univariate analysis a higher level of comorbidity was not associated with worse OS (aa-CCI HR 0.99; [95% CI 0.87–1.13], p = 0.93; ACE-27: HR 0.96; [95% CI 0.79–1.17], p = 0.69). Conclusions. Men with mCRPC, who have comorbidities may benefit from treatment with docetaxel.

scholarly journals Enzalutamide in Metastatic Prostate Cancer Before Chemotherapy

2021 ◽  
pp. 101-106
Author(s):  
Joseph Zabell
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Metastatic Prostate Cancer ◽  
Radiographic Progression ◽  
Progression Free Survival ◽  
Cytotoxic Chemotherapy ◽  
Free Survival ◽  
Prior Chemotherapy ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

This chapter summarizes the findings of the landmark PREVAIL trial conducted in men with castrate-resistant prostate cancer who had received prior chemotherapy comparing enzalutamide to placebo. It demonstrated improved overall survival, radiographic progression-free survival, and time to cytotoxic chemotherapy.

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