Time to disease-related pain after sipuleucel-T in asymptomatic patients with metastatic castrate-resistant prostate cancer (mCRPC): Results from three randomized phase III trials.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 4661-4661 ◽  
Author(s):  
E. J. Small ◽  
C. S. Higano ◽  
P. W. Kantoff ◽  
J. B. Whitmore ◽  
M. W. Frohlich ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Iii ◽  
Asymptomatic Patients ◽  
Phase Iii Trials ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

scholarly journals New Therapeutics to Treat Castrate-Resistant Prostate Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Ömer Acar ◽  
Tarık Esen ◽  
Nathan A. Lack
Keyword(s):  
Prostate Cancer ◽  
Late Stage ◽  
Endocrine Disruptor ◽  
Patient Survival ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Bone Targeting ◽  
Phase Iii Trials ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

The effective treatment of castrate-resistant prostate cancer (CRPC) has proven to be very challenging. Until recently, docetaxel was the only therapeutic demonstrated to extend overall patient survival. Yet recently, a considerable number of new therapeutics have been approved to treat CRPC patients. These remarkable advances now give new tools for the therapeutic management of late-stage prostate cancer. In this review, we will examine mechanistic and clinical data of several newly approved therapeutics including the chemotherapeutic cabazitaxel, antiandrogen enzalutamide, endocrine disruptor abiraterone acetate, immunotherapy sipuleucel-T, and bone-targeting radiopharmaceutical alpharadin. In addition, we will examine other promising therapeutics that are currently in Phase III trials.

scholarly journals Apalutamide in the treatment of castrate-resistant prostate cancer: evidence from clinical trials

2018 ◽  
Vol 10 (12) ◽  
pp. 445-454 ◽  
Author(s):  
Vadim S. Koshkin ◽  
Eric J. Small
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Specific Antigen ◽  
The United States ◽  
Phase Iii ◽  
Metastatic Progression ◽  
Free Survival ◽  
Phase Iii Trials ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

Apalutamide (ARN-509) is a second-generation androgen receptor (AR) antagonist that was developed to inhibit AR-mediated prostate cancer cell proliferation. Following the initial promising clinical efficacy results in phase I and II clinical trials of patients with metastatic castrate-resistant prostate cancer (CRPC), apalutamide has been investigated in several phase III trials. Particular interest has focused on the development of effective therapy for the prevention of disease progression in patients with nonmetastatic (nm or M0) CRPC, especially patients who have a rapid prostate-specific antigen (PSA) doubling time that is indicative of shorter bone metastasis-free survival and associated with significant morbidity and mortality. The results from the phase III SPARTAN trial were recently published and reported a significant benefit of apalutamide relative to placebo in patients with nmCRPC and a high risk of metastatic progression. The study noted marked improvement in the primary endpoint of metastasis-free survival as well as several relevant secondary clinical endpoints, including time to symptomatic progression. These results led to the United States Food and Drug Administration (US FDA) approval of apalutamide in the nmCRPC setting in February 2018. This review summarizes the clinical development of apalutamide, culminating with the pivotal SPARTAN trial as well as other phase III trials which may further expand potential indications for this agent in the near future.

Postdocetaxel treatment for castrate-resistant prostate cancer: The sequential use of abiraterone and cabazitaxe.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 234-234 ◽  
Author(s):  
David Gareth Fackrell ◽  
Nicholas David James ◽  
Daniel Ford
Keyword(s):  
Prostate Cancer ◽  
Survival Benefit ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
Select Group ◽  
Phase Iii Trials ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
The Uk

234 Background: Large phase III trials have shown both abiraterone (Abi) and cabazitaxel (Cbz) to have a survival benefit in patients with metastatic castrate resistant prostate cancer (mCRPC). They are now used routinely throughout the UK in this setting. The mechanisms of resistance of these drugs remain unclear and therefore, their sequential use is less recognised. We present data from patients who have been exposed to both therapies. Methods: In this retrospective study, we searched our own pharmacy databases to identify all patients that had been exposed to both Abi and Cbz. All patients were treated between April 2009 and October 2012. A total of 21 patients were reviewed and clinical data was collected. SPSS software was used to create Kaplan Meier curves. Results: 17 of the 21 patients received Abi before Caz. Median progression free survival for patients on the sequential regimes was 16.9 months (95% Confidence interval: 10.5-23.3). Reviewing the drugs individually found progression free survival was 5.1 months (4.4-6.0 months) with Abi and 7.1 months (5.1-9.1) with Cbz. Conclusions: In a select group of patients who are fit enough to receive both drugs, superior progression free survival is seen than can be expected on one drug alone. The data compares favourably to that seen in the TROPIC study where time to progression on Cbz was 2.8 months. Furthermore, lack of response to one drug did not preclude worthwhile response to the other agent. These findings are consistent with the drugs having separate mechanisms. At this stage the series is not mature enough to draw conclusions on survival benefit. An updated series, involving larger patient numbers, will be presented at the meeting.

Association of health-related quality of life (HRQOL) variations with biological biomarkers for patients with metastatic castrate-resistant prostate cancer (MCRPC) treated by abiraterone/prednisone combination or prednisone.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 54-54
Author(s):  
Morgan Goujon ◽  
Amelie Anota ◽  
Alexandre Frontczak ◽  
Emilie Charton ◽  
Tristan Maurina ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Phase Iii ◽  
Health Related Quality ◽  
Meaningful Improvement ◽  
Related Quality ◽  
Health Related ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

54 Background: A potential link between Health-Related Quality of life (HRQoL) and oncologic outcomes such as overall survival or progression-free survival has been underlined for endocrine therapies in patients with metastatic castrate resistant prostate cancer (mCRPC). Other surrogates such as circulating tumor cells (CTCs) or PSA can be used to evaluate disease control. This study explored the associations between HRQoL and biological biomarkers for patients with mCRPC treated by abiraterone / prednisone or prednisone within registration phase III trial COU-AA-301. Methods: Baseline differences of HRQoL evaluated with FACT-P total score (FACT-P TS) according to biological parameters (including CTCs and PSA) and links between HRQoL's change and variations of these parameters were assessed. The primary objective was to estimate the association between improvement or deterioration in FACT-P TS and the variations of CTCs and PSA. All analyses were conducted using clinically meaningful improvement and deterioration in FACT-P TS and subscales. Results: Among 1130 patients enrolled, 1111 (98.3%) had a baseline FACT-P TS available. At baseline, a favorable CTCs count was associated with higher FACT-P TS compared to unfavorable CTCs (difference in means 8 points, [95% CI, 4 to 12] p < 0.001). At 3 months, there were differences in mean change from baseline FACT-P TS favoring patients with biomarkers response, with clinically meaningful difference for CTCs (12.7 points, [95% CI, 6 to 19.5%] p < 0.001) and PSA (11.64 points, [95% CI, 9.3 to 14] p < 0.0001). Biological progression was associated with higher risk of FACT-P TS worsening for PSA (Odds Ratio (OR) 2.8 [95% CI, 1.9 to 4.2]) with more frequent FACT-P TS improvement in case of response for CTCs (OR 3.14 [95% CI, 1.3 to 7.7]) and PSA (OR 2.9 [95% CI 2.1 to 4]). Significantly longer time until definitive deterioration was observed for patients with CTCs or PSA response (p < 0.001) and shorter time in case of progression (p < 0.001). Conclusions: QUA-lify is the first study to show an association between HRQoL and biomarkers outcomes in patients with mCRPC treated with endocrine therapy in a post-taxane setting. This concept is reinforced by the consistency of the association for all analyses carried out.

scholarly journals Heterogeneous ensembles for predicting survival of metastatic, castrate-resistant prostate cancer patients

F1000Research ◽  
2017 ◽  
Vol 5 ◽  
pp. 2676 ◽  
Author(s):  
Sebastian Pölsterl ◽  
Pankaj Gupta ◽  
Lichao Wang ◽  
Sailesh Conjeti ◽  
Amin Katouzian ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Survival Analysis ◽  
Ensemble Methods ◽  
Phase Iii ◽  
Survival Models ◽  
Phase Iii Clinical Trials ◽  
Wide Range ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Heterogeneous Ensemble

Ensemble methods have been successfully applied in a wide range of scenarios, including survival analysis. However, most ensemble models for survival analysis consist of models that all optimize the same loss function and do not fully utilize the diversity in available models. We propose heterogeneous survival ensembles that combine several survival models, each optimizing a different loss during training. We evaluated our proposed technique in the context of the Prostate Cancer DREAM Challenge, where the objective was to predict survival of patients with metastatic, castrate-resistant prostate cancer from patient records of four phase III clinical trials. Results demonstrate that a diverse set of survival models were preferred over a single model and that our heterogeneous ensemble of survival models outperformed all competing methods with respect to predicting the exact time of death in the Prostate Cancer DREAM Challenge.

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.

Survival after sipuleucel-T (SIP-T) and low-dose ipilimumab (IPI) in men with metastatic, progressive, castrate-resistant prostate cancer (M-CRPC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 368-368 ◽  
Author(s):  
Justine Ku ◽  
Kirk Wilenius ◽  
Claire Larsen ◽  
Kyle De Guzman ◽  
Steven Yoshinaga ◽  
...  
Keyword(s):  
Median Survival ◽  
Gleason Score ◽  
Low Dose ◽  
Phase Iii ◽  
Combination Methods ◽  
Radium 223 ◽  
Potential Synergy ◽  
Phase Iii Trials ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

368 Background: Phase III trials evaluating enzalutamide or abiraterone in MP-CRPC prior to docetaxel report a median survival of 35 months. SIP-T functions by stimulating cancer-specific dendritic cells and prolongs survival. IPI showed a borderline survival advantage in a large randomized trial. Thus, there may be potential synergy with SIP-T and IPI (SIPIPI) in combination. Methods: Between April 2013 and April 2014, 9 docetaxel-naive men with MP-CRPC were treated prospectively with SIP-T followed immediately by low-dose IPI 1 mg/kg given for a total of 1 to 3 doses every three weeks. As has been previously published (Immuno Targets and Therapy, March 2017), cancer-specific immunoglobulins (IGS) directed at PA2024 and PAP showed a statistically-significant increase after SIP-T and a further statistically-significant increase, above the level achieved with SIP-T, after IPI. Three patients died from progressive disease after 9, 18, and 20 months. This abstract updates the outcome and survival of the remaining 6 patients. Results: Adverse events from SIPIPI were negligible. For the 9 men, the median age, Gleason score, and number of previous hormonal interventions were 77 years, 8, and 3, respectively. Median baseline PSA and Gleason score were 1.7 and 8, respectively. Eight men had bone metastases and 1 had lymph node metastasis. For the 6 surviving men, median follow-up since SIPIPI is 50.5 months (40-53). Their median PSA as of September 2017 is 5.5 (range: 0.27–18.10). Further treatment since SIPIPI includes abiraterone (4) enzalutamide (5) radium-223 (3) docetaxel (2) cabazitaxel (1) carboplatin (1) pembrolizumab (2) and Olaparib (1). One patient continues with a stable PSA of 0.27 without any further treatment post SIPIPI except SBRT. Conclusions: In this small trial of SIPIPI performed in men with docetaxel-naive MP-CRPC, median survival has now surpassed 4 years and the 6 surviving men still maintain a relatively low median PSA of 5.5. One man continues in durable remission without any further therapy except SBRT administered immediately post IPI.

scholarly journals Heterogeneous ensembles for predicting survival of metastatic, castrate-resistant prostate cancer patients

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2676 ◽  
Author(s):  
Sebastian Pölsterl ◽  
Pankaj Gupta ◽  
Lichao Wang ◽  
Sailesh Conjeti ◽  
Amin Katouzian ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Survival Analysis ◽  
Ensemble Methods ◽  
Phase Iii ◽  
Survival Models ◽  
Phase Iii Clinical Trials ◽  
Wide Range ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Heterogeneous Ensemble

Ensemble methods have been successfully applied in a wide range of scenarios, including survival analysis. However, most ensemble models for survival analysis consist of models that all optimize the same loss function and do not fully utilize the diversity in available models. We propose heterogeneous survival ensembles that combine several survival models, each optimizing a different loss during training. We evaluated our proposed technique in the context of the Prostate Cancer DREAM Challenge, where the objective was to predict survival of patients with metastatic, castrate-resistant prostate cancer from patient records of four phase III clinical trials. Results demonstrate that a diverse set of survival models were preferred over a single model and that our heterogeneous ensemble of survival models outperformed all competing methods with respect to predicting the exact time of death in the Prostate Cancer DREAM Challenge.

scholarly journals Heterogeneous ensembles for predicting survival of metastatic, castrate-resistant prostate cancer patients

F1000Research ◽  
2017 ◽  
Vol 5 ◽  
pp. 2676 ◽  
Author(s):  
Sebastian Pölsterl ◽  
Pankaj Gupta ◽  
Lichao Wang ◽  
Sailesh Conjeti ◽  
Amin Katouzian ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Survival Analysis ◽  
Ensemble Methods ◽  
Phase Iii ◽  
Survival Models ◽  
Phase Iii Clinical Trials ◽  
Wide Range ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Heterogeneous Ensemble

Ensemble methods have been successfully applied in a wide range of scenarios, including survival analysis. However, most ensemble models for survival analysis consist of models that all optimize the same loss function and do not fully utilize the diversity in available models. We propose heterogeneous survival ensembles that combine several survival models, each optimizing a different loss during training. We evaluated our proposed technique in the context of the Prostate Cancer DREAM Challenge, where the objective was to predict survival of patients with metastatic, castrate-resistant prostate cancer from patient records of four phase III clinical trials. Results demonstrate that a diverse set of survival models were preferred over a single model and that our heterogeneous ensemble of survival models outperformed all competing methods with respect to predicting the exact time of death in the Prostate Cancer DREAM Challenge.

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