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.

Androgen pathway constitutional polymorphism predictors of progression-free and overall survivals in advanced castrate-resistant prostate cancer (CRPC) patients treated with ketoconazole (KC).

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 54-54
Author(s):  
T. L. Davis ◽  
J. Jung ◽  
K. A. Carr ◽  
S. Philips ◽  
Y. Mohammadi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Cancer Center ◽  
Indiana University ◽  
Hormone Synthesis ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Hormonal Therapies ◽  
Ecog Ps

54 Background: Recent trials have highlighted the clinical utility of second-line hormonal therapies for CRPC. KC, an oral inhibitor of CYP3A4 and CYP17, is commonly used in this setting. Germline SNPs in genes critical to hormone synthesis, transport, metabolism, binding sites, and degradation may contribute to variability in outcomes observed in KC treated CRPC pts. Methods: Between 1/07 and 10/08, all PCa pts seen in the Indiana University Simon Cancer Center oncology clinics were approached for recruitment to the Prostate Cancer Genetic Risk Evaluation of SNPs Study (PROGRESS). Participants completed a demographic and clinical questionnaire and provided a peripheral blood sample. Only pts with initiated on KC were included in this analysis. Germline DNA was analyzed for SNP genotyping on a 128-SNP chip using a TaqMan OpenArray GT Kit. The chip included genes critical to hormone signaling, transport, and elimination pathways with minor allele frequencies > 5%. Pts were followed for progression-free survival (PFS) and overall survival (OS) endpoints. Univariable analyses were performed to identify significant associations between SNP genotype, clinical parameters, and PFS and OS outcomes. Results: Between January 2007 and October 2008, 39 pts with CRPC initiated on KC therapy enrolled. Demographics included: age (median) – 70 yrs, prostate specific antigen (PSA) (median) – 13.0 ng/ml, PSA doubling time (median) – 2.9 months, metastatic –85%, ECOG PS 0– 74%. Age < 70 was associated with shorter PFS (p=0.010) and age > 70 was associated with shorter OS (p=0.030). SNPs significantly associated with PFS and OS are summarized in the table. Conclusions: Interpatient differences in hormonal pathway germline SNPs may contribute to variability in clinical outcomes in pts treated with KC. [Table: see text] No significant financial relationships to disclose.

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.

Phase Ib study assessing different sequencing regimens of atezolizumab (anti-PD-L1) and sipuleucel-T (SipT)in patients who have asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17564-e17564 ◽  
Author(s):  
Charles Joel Rosser ◽  
Yosuke Hirasawa ◽  
Jared David Acoba ◽  
David Jon Tamura ◽  
Sumanta K. Pal ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Vaccine ◽  
Objective Response ◽  
Median Number ◽  
Phase Ib ◽  
Grade 5 ◽  
Castrate Resistant Prostate Cancer ◽  
Grade 3 ◽  
Castrate Resistant ◽  
Ecog Ps

e17564 Background: Combining an immune checkpoint inhibitor with a tumor vaccine may leverage complementary mechanisms of action for treatment of mCRPC. Atezolizumab, a fully human anti–PD-L1 IgG1 antibody, is an approved treatment option in multiple indications; while SipT, an autologous cellular immunotherapeutic, is approved for treatment of metastatic castrate resistant prostate cancer (mCRPC). We present a phase Ib study evaluating safety, tolerability and objective response rate of atezolizumab + SipT in patients with mCRPC (NCT03024216). Methods: Eligible patients who had asymptomatic or minimally symptomatic progressive mCRPC and met standard criteria for sipuleucel-T were randomized to receive either atezolizumab 1200 mg IV every 3 weeks for 2 doses then SipT IV every 2 weeks for a total of three infusions (Arm 1) or SipT IV every 2 weeks for a total of three infusions followed by atezolizumab 1200 mg IV every 3 weeks for 2 doses (Arm 2). The primary endpoint was safety, while secondary endpoints included objective tumor response (PCWG2 and modified RECISTv1.1 criteria) and comparing systemic immune responses after induction between the arms. Results: As of February 6, 2020, 37 pts (median follow-up 7.4 months, median age 75 yrs [range 53.0–86.0]; median number of previous treatments 4 [range 1-8], 75.7% ECOG PS = 0) were enrolled. Three patients did not complete induction therapy (1 – withdrew consent, 1 developed toxicity, and 1 progressed). There were no grade 5 toxicities attributed to study drugs and grade 4 toxicities were noted in 2 patients, 1 in each arm (Arm 1 bronchitis and Arm 2 hypotension). Eight grade 3 toxicities were noted in arm 1 (hyponatremia, pulmonary embolus x3, bone pain, hypophosphatemia, shock, tooth fracture from a fall), while 4 grade 3 toxicities were noted in arm 2 (anemia, hypertension x 2, pneumonia). None of the grade 3 or 4 SAEs were noted to be irAEs. At 6 months, there were 11 SD (7 in Arm 1 and 4 in Arm 2), 18 PD and 7 unevaluable (3 withdrew from study and 4 have yet to reach 6 month evaluation). At this time, PFS was noted to be 8.2 months in Arm 1 and 5.8 months in Arm 2 (p = 0.054). Conclusions: The safety profile of the combination of atezolizumab with sipuleucel-T appears manageable in a heavily pre-treated population and consistent with those agents administered as monotherapy. Responses were seen but no CR. Immune activation studies may shed light on which sequence is optimal. Clinical trial information: NCT03024216 .

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.

An analysis of survival in patients with castrate-resistant prostate cancer receiving enzalutamide with treatment breaks

2021 ◽  
pp. 205141582199376
Author(s):  
Michael P Rowe ◽  
Stuart Walter ◽  
Ayesha Hidayat ◽  
Adam Pollard ◽  
Timothy Norris ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Time ◽  
Specific Antigen ◽  
Median Number ◽  
Start Time ◽  
Level Of Evidence ◽  
Significance Level ◽  
Castrate Resistant Prostate Cancer ◽  
Prospective Trials ◽  
Castrate Resistant

Objective: Enzalutamide is effective in treating metastatic castrate-resistant prostate cancer (mCRPC) but can have side effects that require treatment breaks (TB). We conducted a retrospective analysis of outcomes of patients who had extended TB due to toxicity compared to continuous dosing. Methods: Patients prescribed enzalutamide for mCRPC from September 2011 to February 2018 were included. TB was defined as an interruption of four weeks or more. Overall survival (OS) from enzalutamide start, time to prostate-specific antigen failure (TTF) and total enzalutamide treatment time (TTT) were analysed for TB and continuous responders (>50% PSA drop), and a significance level of 0.05 was assigned. Results: A total of 110 patients were continuous responders, and 29 had TB. The median number of interruptions was one (range 1–7), and time on treatment was 70% in the TB group. The TB group had significantly improved OS (100 vs. 60 months; hazard ratio=1.8, 95% confidence interval 1.17–2.77, p=0.02), prolonged TTF (median 11 vs. 6 months; p=0.008) and TTT (median 15 vs. 8 months; p=0.0001). Conclusion: Extended TB do not seem to impact OS or treatment duration adversely in patients who are responding and experiencing toxicity, and may be a useful option in managing toxicity. Prospective trials could explore this further. Level of evidence: Level 2c.

scholarly journals Cabazitaxel versus abiraterone or enzalutamide in metastatic castration-resistant prostate cancer: post hoc analysis of the CARD study excluding chemohormonal therapy for castrate-naive disease

2021 ◽  
Author(s):  
Hiroyoshi Suzuki ◽  
Daniel Castellano ◽  
Johann de Bono ◽  
Cora N Sternberg ◽  
Karim Fizazi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Clinical Outcomes ◽  
Specific Antigen ◽  
Tumour Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Number Of Cycles

Abstract Background In the CARD study (NCT02485691), cabazitaxel significantly improved clinical outcomes versus abiraterone or enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel and the alternative androgen-signalling-targeted inhibitor. However, some patients received docetaxel or the prior alternative androgen-signalling-targeted inhibitor in the metastatic hormone-sensitive (mHSPC) setting. Therefore, the CARD results cannot be directly translated to a Japanese population. Methods Patients (N = 255) received cabazitaxel (25 mg/m2 IV Q3W, prednisone, G-CSF) versus abiraterone (1000 mg PO, prednisone) or enzalutamide (160 mg PO) after prior docetaxel and progression ≤12 months on the alternative androgen-signalling-targeted inhibitor. Patients who received combination therapy for mHSPC were excluded (n = 33) as docetaxel is not approved in this setting in Japan. Results A total of 222 patients (median age 70 years) were included in this subanalysis. Median number of cycles was higher for cabazitaxel versus androgen-signalling-targeted inhibitors (7 versus 4). Clinical outcomes favoured cabazitaxel over abiraterone or enzalutamide including, radiographic progression-free survival (rPFS; median 8.2 versus 3.4 months; P &lt; 0.0001), overall survival (OS; 13.9 versus 11.8 months; P = 0.0102), PFS (4.4 versus 2.7 months; P &lt; 0.0001), confirmed prostate-specific antigen response (37.0 versus 14.4%; P = 0.0006) and objective tumour response (38.9 versus 11.4%; P = 0.0036). For cabazitaxel versus androgen-signalling-targeted inhibitor, grade ≥ 3 adverse events occurred in 55% versus 44% of patients, with adverse events leading to death on study in 2.7% versus 5.7%. Conclusions Cabazitaxel significantly improved outcomes including rPFS and OS versus abiraterone or enzalutamide and are reflective of the Japanese patient population. Cabazitaxel should be considered the preferred treatment option over abiraterone or enzalutamide in this setting.

scholarly journals In vitro engineering of a bone metastases model allows for study of the effects of antiandrogen therapies in advanced prostate cancer

2021 ◽  
Vol 7 (27) ◽  
pp. eabg2564
Author(s):  
Nathalie Bock ◽  
Thomas Kryza ◽  
Ali Shokoohmand ◽  
Joan Röhl ◽  
Akhilandeshwari Ravichandran ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Advanced Prostate Cancer ◽  
Adaptive Responses ◽  
Metastatic Tissue ◽  
Metastatic Lesions ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

While androgen-targeted therapies are routinely used in advanced prostate cancer (PCa), their effect is poorly understood in treating bone metastatic lesions and ultimately results in the development of metastatic castrate resistant prostate cancer (mCRPC). Here, we used an all-human microtissue-engineered model of mineralized metastatic tissue combining human osteoprogenitor cells, 3D printing and prostate cancer cells, to assess the effects of the antiandrogens, bicalutamide, and enzalutamide in this microenvironment. We demonstrate that cancer/bone stroma interactions and antiandrogens drive cancer progression in a mineralized microenvironment. Probing the bone microenvironment with enzalutamide led to stronger cancer cell adaptive responses and osteomimicry than bicalutamide. Enzalutamide presented with better treatment response, in line with enzalutamide delaying time to bone-related events and enzalutamide extending survival in mCRPC. The all-human microtissue-engineered model of mineralized metastatic tissue presented here represents a substantial advance to dissect the role of the bone tumor microenvironment and responses to therapies for mCPRC.

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.

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