scholarly journals From Bench to Bedside: Immunotherapy for Prostate Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Brian Wan-Chi Tse ◽  
Lidija Jovanovic ◽  
Colleen Coyne Nelson ◽  
Paul de Souza ◽  
Carl Andrew Power ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Current Treatment ◽  
Phase Iii ◽  
Rational Approach ◽  
Targeting Therapy ◽  
Treatment Regimes ◽  
Radium 223 ◽  
Clinical Benefits ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

The mainstay therapeutic strategy for metastatic castrate-resistant prostate cancer (CRPC) continues to be androgen deprivation therapy usually in combination with chemotherapy or androgen receptor targeting therapy in either sequence, or recently approved novel agents such as Radium 223. However, immunotherapy has also emerged as an option for the treatment of this disease following the approval of sipuleucel-T by the FDA in 2010. Immunotherapy is a rational approach for prostate cancer based on a body of evidence suggesting these cancers are inherently immunogenic and, most importantly, that immunological interventions can induce protective antitumour responses. Various forms of immunotherapy are currently being explored clinically, with the most common being cancer vaccines (dendritic-cell, viral, and whole tumour cell-based) and immune checkpoint inhibition. This review will discuss recent clinical developments of immune-based therapies for prostate cancer that have reached the phase III clinical trial stage. A perspective of how immunotherapy could be best employed within current treatment regimes to achieve most clinical benefits is also provided.

scholarly journals Radium-223 Therapy for Patients with Metastatic Castrate-Resistant Prostate Cancer: An Update on Literature with Case Presentation

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Nghi C. Nguyen ◽  
Muhammad Shah ◽  
Leonard J. Appleman ◽  
Rahul Parikh ◽  
James M. Mountz
Keyword(s):  
Prostate Cancer ◽  
Single Agent ◽  
Chemotherapeutic Agents ◽  
Research Data ◽  
Phase Iii ◽  
Radium 223 ◽  
Bayer Healthcare ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Case Presentations

Background and Purpose. Radium-223 dichloride (Xofigo®, Bayer HealthCare Pharmaceuticals Inc.) is the first α-particle emitter therapeutic agent approved by the FDA, with benefits in overall survival and delay in symptomatic skeletal event for patients with metastatic castrate-resistant prostate cancer (CRPC). Recent post hoc analyses of the phase III ALSYMPCA trial support the previously established safety profile as well as therapeutic effect and clinical outcome of Radium-223. Currently, Radium-223 is approved as a single agent therapy for metastatic CRPC. Clinical trials are currently investigating Radium-223 in additional clinical settings such as earlier asymptomatic disease and in combination with other agents including hormonal therapeutic agents and immunotherapeutic as well as chemotherapeutic agents. Trials are also ongoing in patients with other primary cancers such as breast cancer, thyroid cancer, and renal cancer metastatic to bone. In this article, the physics and radiobiology, as well as a literature update on the use of Radium-223, are provided along with case presentations, aiming at a better appreciation of research data as well as the assimilation of research data into clinical practice.

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.

scholarly journals Titration of Androgen Signaling: How Basic Studies Have Informed Clinical Trials Using High-Dose Testosterone Therapy in Castrate-Resistant Prostate Cancer

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 884
Author(s):  
Steven K. Nordeen ◽  
Lih-Jen Su ◽  
Gregory A. Osborne ◽  
Perry M. Hayman ◽  
David J. Orlicky ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Dose ◽  
Castration Resistant Prostate Cancer ◽  
Androgen Ablation ◽  
Clinical Observations ◽  
Clinical Benefits ◽  
Castrate Resistant Prostate Cancer ◽  
Prostate Cancers ◽  
Castrate Resistant ◽  
Basic Studies

Since the Nobel Prize-winning work of Huggins, androgen ablation has been a mainstay for treatment of recurrent prostate cancer. While initially effective for most patients, prostate cancers inevitably develop the ability to survive, grow, and metastasize further, despite ongoing androgen suppression. Here, we briefly review key preclinical studies over decades and include illustrative examples from our own laboratories that suggest prostate cancer cells titrate androgen signaling to optimize growth. Such laboratory-based studies argue that adaptations that allow growth in a low-androgen environment render prostate cancer sensitive to restoration of androgens, especially at supraphysiologic doses. Based on preclinical data as well as clinical observations, trials employing high-dose testosterone (HDT) therapy have now been conducted. These trials suggest a clinical benefit in cancer response and quality of life in a subset of castration-resistant prostate cancer patients. Laboratory studies also suggest that HDT may yet be optimized further to improve efficacy or durability of response. However, laboratory observations suggest that the cancer will inevitably adapt to HDT, and, as with prior androgen deprivation, disease progression follows. Nonetheless, the adaptations made to render tumors resistant to hormonal manipulations may reveal vulnerabilities that can be exploited to prolong survival and provide other clinical benefits.

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.

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