Causes of death in intermediate- and high-risk prostate cancer treated with radiotherapy with or without androgen deprivation therapy: Analysis from two phase III trials.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 34-34
Author(s):  
Abdenour Nabid ◽  
Nathalie Carrier ◽  
Eric Vigneault ◽  
André-Guy Martin ◽  
Luis Souhami ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
High Risk ◽  
Statistical Difference ◽  
Causes Of Death ◽  
Phase Iii ◽  
Second Cancer ◽  
Two Phase ◽  
Phase Iii Trials

34 Background: The purpose of this analysis was to establish causes of death in a population of intermediate-risk (IR) and high-risk (HR) prostate cancer treated on two phase III trials. Methods: From October 2000 to September 2010, 1,230 patients were randomized: 630 with HR (ClinicalTrials.gov, #NCT00223171) and 600 with IR (#NCT00223145). HR was defined as T3-4, PSA >20 g/ml, Gleason >7 (with at least one of these 3 factors). IR was defined as T1-T2, Gleason < 6 and PSA 10-20 ng/ml or T1-T2, Gleason 7 and PSA < 20 ng/ml. Causes of death were compiled until July 2015 and were established from data sent by the different investigators and centrally reviewed. Causes of death were mainly based on data from clinical records, then by family members, obituaries, death certificates and family physicians. Results: The median follow-up for the 1,230 patients was 7.5 years (HR 8 vs. IR 6.8 years, p<0.001). 30.2% (372/1,230) patients had died: (HR 37% vs. IR 23.2%, p<0.001). A total of 8% (99/1,230) patients developed local, regional, and metastatic prostate cancer recurrences: (HR 11.6% vs. IR 4.3%, p<0.001) and 4.4% (54/1,230) died from prostate cancer: (HR 7.3% vs. IR 1.3%, p<0.001). The most frequent cause of death was a second cancer (120/1,230, 9.8%): (HR 10.6% vs. IR 8.8%, p=NS). Cardiovascular deaths occurred in 6.3% (78/1,230) (HR 7.1% vs. IR 5.5%, p=NS) with no statistical difference between the different durations of androgen deprivation therapy (ADT) 0, 6, 18, or 36 months. Other causes of death were pulmonary (3.7%), digestive (1.1%), others (3.3%), and unknown (1.7%). Majority of deaths occurred between 3 and 9 years after randomization (HR 70% and IR 73%). Prostate cancer deaths were distributed over all the follow-up period. The 5/10 year overall survival between HR and IR were 88.6%, 91.8%, and 61.6%, 69.8%, respectively with significant differences (p=0.045 and p=0.016). Conclusions: In patients with localized HR and IR prostate cancer, the first cause of death was a second cancer and prostate cancer came as the third one after cardiovascular disease. There was no statistical difference in the incidence of cardiovascular deaths in patients treated with different durations of ADT. Clinical trial information: Clinical Trials, gov. #NCT00223145 - Clinical Trials, gov. #NCT00223171.

Causes of death in localised prostate cancer: Long term data from two phase III trials

2018 ◽  
Vol 17 (2) ◽  
pp. e1832
Author(s):  
A. Nabid ◽  
N. Carrier ◽  
É. Vigneault ◽  
C. Lemaire ◽  
M.-A. Brassard ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Causes Of Death ◽  
Phase Iii ◽  
Two Phase ◽  
Phase Iii Trials ◽  
Term Data

Therapeutic Vaccines and Immunotherapy in Castration-Resistant Prostate Cancer: Current Progress and Clinical Applications

2013 ◽  
pp. e166-e170
Author(s):  
James L. Gulley ◽  
Ravi A. Madan ◽  
Christopher R. Heery
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Cancer Vaccine ◽  
Therapeutic Vaccine ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Two Phase ◽  
Therapeutic Vaccines ◽  
Therapeutic Cancer Vaccine ◽  
Phase Iii Trials

Results of recent clinical trials have intensified interest in immunotherapy for cancer. Among the most promising candidates for immunotherapy are patients with prostate cancer. Results of therapeutic vaccine clinical trials in this population have suggested statistically significant and clinically meaningful improvements in overall survival, with substantially fewer side effects than with chemotherapy. Of particular interest are sipuleucel-T, the first U.S. Food and Drug Administration-approved therapeutic cancer vaccine, and PSA-TRICOM (PROSTVAC), a therapeutic cancer vaccine in phase III testing. The immune checkpoint inhibitor ipilimumab is also stirring considerable interest, with two phase III trials ongoing in prostate cancer. This article highlights data emerging from these trials and addresses remaining questions and practical clinical implications of this therapeutic strategy.

scholarly journals A Review of Phase III Clinical Trials of Prostate Cancer Chemoprevention

2007 ◽  
Vol 89 (3) ◽  
pp. 207-211 ◽  
Author(s):  
JF Thorpe ◽  
S Jain ◽  
TH Marczylo ◽  
AJ Gescher ◽  
WP Steward ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Cancer Prevention ◽  
Age Of Onset ◽  
Cancer Chemoprevention ◽  
Phase Iii ◽  
Phase Iii Clinical Trials ◽  
Prostate Cancer Prevention ◽  
Phase Iii Trials

INTRODUCTION Prostate cancer is an excellent target for chemoprevention strategies; given its late age of onset, any delay in carcinogenesis would lead to a reduction in its incidence. This article reviews all the completed and on-going phase III trials in prostate cancer chemoprevention. PATIENTS AND METHODS All phase III trials of prostate cancer chemoprevention were identified within a Medline search using the keywords ‘clinical trial, prostate cancer, chemoprevention’. RESULTS In 2003, the Prostate Cancer Prevention Trial (PCPT) became the first phase III clinical trial of prostate cancer prevention. This landmark study was terminated early due to the 24.8% reduction of prostate cancer prevalence over a 7-year period in those men taking the 5α-reductase inhibitor, finasteride. This article reviews the PCPT and the interpretation of the excess high-grade prostate cancer (HGPC) cases in the finasteride group. The lack of relationship between cumulative dose and the HGPC cases, and the possible sampling error of biopsies due to gland volume reduction in the finasteride group refutes the suggestion that this is a genuine increase in HGPC cases. The other on-going phase III clinical trials of prostate cancer chemoprevention – the REDUCE study using dutasteride, and the SELECT study using vitamin E and selenium – are also reviewed. CONCLUSIONS At present, finasteride remains the only intervention shown in long-term prospective phase III clinical trials to reduce the incidence of prostate cancer. Until we have the results of trials using alternative agents including the on-going REDUCE and SELECT trials, the advice given to men interested in prostate cancer prevention must include discussion of the results of the PCPT. The increased rate of HGPC in the finasteride group continues to generate debate; however, finasteride may still be suitable for prostate cancer prevention, particularly in men with lower urinary tract symptoms.

scholarly journals Evaluating Intermittent Androgen-Deprivation Therapy Phase III Clinical Trials: The Devil Is in the Details

2016 ◽  
Vol 34 (3) ◽  
pp. 280-285 ◽  
Author(s):  
Maha Hussain ◽  
Catherine Tangen ◽  
Celestia Higano ◽  
Nicholas Vogelzang ◽  
Ian Thompson
Keyword(s):  
Prostate Cancer ◽  
Statistical Power ◽  
Progression Free Survival ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
End Point ◽  
Phase Iii Clinical Trials ◽  
Noninferiority Trials ◽  
Phase Iii Trials

Purpose Intermittent androgen deprivation (IAD) has been widely tested in prostate cancer. However, phase III trials testing continuous androgen deprivation (CAD) versus IAD have reached inconclusive and seemingly contradictory results. Different design and conduct issues must be critically evaluated to better interpret the results. Patients and Methods Seven published phase III trials were examined for prespecified design and outcomes. Treatment specifications; primary end point; superiority versus noninferiority design assumptions, including magnitude of assumed versus observed noninferiority margin (NIM); duration of follow-up; and quality-of-life (QOL) outcomes were considered in terms of the results and conclusions reported. Results Five trials had a superiority and three had a noninferiority primary hypothesis. Only three trials had a uniform population and overall survival (OS) end point. All trials observed better outcomes in terms of OS and progression-free survival (PFS) than assumed at time of study design, translating into prespecified NIMs or hazard ratios that reflected larger absolute differences in OS or PFS between arms. Lower-than-expected event rates also reduced statistical power for the trials. Other factors, including length of follow-up, cause of death, QOL, and primary end point, and their impact on trial interpretation are discussed. Conclusion No trial to date has demonstrated survival superiority of IAD compared with CAD. Trials concluding IAD is noninferior to CAD were based on wide NIMs that included clinically important survival differences, not likely to be considered comparable by physicians or patients. Interim analyses relying on short follow-up and including a majority of non–prostate cancer deaths will favor a noninferiority conclusion and should be interpreted cautiously. Adequate follow-up is required to ensure capture of prostate cancer deaths in both superiority and noninferiority trials.

A phase III protocol of androgen suppression (AS) and 3DCRT/IMRT versus AS and 3DCRT/IMRT followed by chemotherapy (CT) with docetaxel and prednisone for localized, high-risk prostate cancer (RTOG 0521).

2015 ◽  
Vol 33 (18_suppl) ◽  
pp. LBA5002-LBA5002 ◽  
Author(s):  
Howard M. Sandler ◽  
Chen Hu ◽  
Seth A. Rosenthal ◽  
Oliver Sartor ◽  
Leonard G. Gomella ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Type I ◽  
Current Standard ◽  
T Stage

LBA5002 Background: High-risk, localized prostate cancer (PCa) patients have a relatively poor prognosis. We hypothesized that the addition of adjuvant docetaxel and prednisone to long-term (24 month) AS and radiation therapy (RT) would improve overall survival (OS). Methods: RTOG 0521 opened December 2005 and closed August 2009 with targeted accrual of 600 cases. It was designed to detect improvement in 4-year OS from 86% to 93% with a 51% hazard reduction (HR = 0.49). Under a 0.05 1-sided type I error and 90% power, at least 78 deaths were required to analyze the OS endpoint. Patients had 1) Gleason (Gl) 7-8, any T-stage, and PSA > 20, or 2) Gl 8, ≥ T2, any PSA, or 3) Gl 9-10, any T-stage, any PSA. All had PSA ≤ 150. RT dose was 75.6 Gy. CT consisted of 6, 21-day cycles of docetaxel + prednisone starting 28 days after RT. Results: Of 612 enrolled, 50 were excluded for eligibility issues, leaving 562 evaluable. Median age = 66, median PSA = 15.1, 53% had Gl 9-10, 27% had cT3-4. Median follow-up = 5.5 yrs. 4-yr OS rates were 89% [95% CI: 84-92%] for the AS+RT arm and 93% [95% CI: 90-96%] for the AS+RT+CT arm (1-sided p = 0.03, HR = 0.68 [95% CI: 0.44, 1.03]). There were 52 centrally-reviewed deaths in the AS+RT arm and 36 in the AS+RT+CT arm, with fewer deaths both due to PCa/treatment (20 vs 16) and due to other causes/unknown (32 vs 20) in the AS+RT+CT arm. 5-yr disease-free survival rates were 66% for AS+RT and 73% for AS+RT+CT (2-sided p = 0.05, HR = 0.76 [95% CI: 0.57, 1.00]). There was 1, Gr 5 unlikely-related adverse event (AE) in the AS+RT arm and 2, Gr 5 possibly/probably-related AEs with AS+RT+CT. Conclusions: For high-risk, localized PCa, adjuvant CT improved the OS from 89% to 93% at 4 years. Toxicity was acceptable. This trial was designed with a short OS assessment period and additional follow-up is warranted to determine the long-term benefit of CT to the current standard of care of long-term AS+RT. This project was supported by grants U10CA21661, U10CA180868, U10CA180822, from the National Cancer Institute and Sanofi with additional support from AstraZeneca for Australian site participation. Clinical trial information: NCT00288080.

Contemporary treatment patterns and short-term outcomes in men with very high-risk prostate cancer.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 103-103
Author(s):  
Jeffrey J. Tosoian ◽  
Debasish Sundi ◽  
Brian Francis Chapin ◽  
Emmanuel S. Antonarakis ◽  
Meera Chappidi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Lymph Node ◽  
High Risk ◽  
Local Treatment ◽  
Treatment Patterns ◽  
Short Term ◽  
Gleason Pattern ◽  
Very High

103 Background: Beginning in 2014, the National Comprehensive Cancer Network (NCCN) recognized very high-risk (VHR) prostate cancer (cT3b-T4, or primary Gleason pattern 5, or more than 4 biopsy cores with Gleason score 8-10, or multiple HR features) as a classification distinct from high-risk (HR) disease. Using prospectively collected institutional data, we describe contemporary treatment patterns and short-term outcomes in the VHR population. Methods: Men who underwent radical prostatectomy (RP) between January 2010 and June 2015 were identified using the Johns Hopkins RP database, and trends in management were compared across the study period. Pathological and short-term clinical outcomes were assessed in men with VHR cancer. Non organ-confined disease (NOCD) was defined as ≥ pT3 disease or lymph node positivity, persistent postoperative PSA as ≥ 0.2 ng/mL, and biochemical recurrence (BCR) as a PSA ≥ 0.2 ng/mL following an initial undetectable postoperative PSA. Results: During the study period, 4,954 men underwent RP, of which 161 (3.2%) men had VHR cancer at diagnosis. The annual proportion of men who underwent RP with VHR cancer increased over the study period (chronologically 1.8%, 1.0%, 3.3%, 4.1%, 5.6%, and 5.2%; p<0.001). Sixteen percent of men with VHR disease were enrolled in pre-surgical clinical trials, with an increase from 0% of men in 2010 to 19.1% in 2015 (p=0.11). At RP, 39% of the VHR cohort had seminal vesicle invasion, 26% had lymph node involvement, and a total of 74% had NOCD. Following surgery, 33% of men had PSA persistence, and 40% experienced either PSA persistence or BCR during follow-up (median 13.4 months). Of 136 men with at least one follow-up assessment, 15 (11.0%) developed metastasis; 33% of the cohort was treated with radiation therapy, 42% with androgen deprivation, and 15% with docetaxel. Conclusions: The VHR population carries the greatest risk of clinical progression following local treatment. Over the past five years, we have observed increasing surgical treatment and clinical trial enrollment at our institution. Continued assessment of post-operative interventions and outcomes will help to facilitate counseling and establish point estimates from which to power clinical trials.

Evaluation and follow-up of patients with n1-3 m0 or nxm1 prostate cancer in phase iii trials

Urology ◽  
1997 ◽  
Vol 49 (4) ◽  
pp. 39-45 ◽  
Author(s):  
Reginald Hall ◽  
Per Olov Hedlund ◽  
Rolf Ackermann ◽  
Nicholas Bruchovsky ◽  
Otilia Dalesio ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Iii ◽  
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.

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