Influence of CHAARTED, STAMPEDE, and LATITUDE eligibility criteria on utilization of abiraterone (A) and docetaxel (D).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 301-301
Author(s):  
Shruti Parshad ◽  
Urban Emmenegger
Keyword(s):  
Prostate Cancer ◽  
Treatment Duration ◽  
Medical Oncology ◽  
High Volume ◽  
Patient Characteristics ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Drug Access ◽  
Low Volume ◽  
Phase Iii Studies

301 Background: A and D improve the survival of men with high-risk localized or metastatic hormone-naïve prostate cancer (HNPC) when combined with androgen deprivation therapy (ADT). However, the two drugs differ regarding side effects, treatment duration, and associated costs. Furthermore, different eligibility criteria were used in the seminal phase III studies. Since the latter may impact on drug access in many constituencies, we decided to study how applying the eligibility criteria of CHAARTED, STAMPEDE and LATITUDE for drug funding purposes might influence the utilization of A versus D. Methods: 102 men with HNPC were referred from 06/2014 to 09/2017 to the medical oncology service at Odette Cancer Centre (Toronto/ON, Canada) for consideration of additional systemic therapy secondary to ADT. After extraction of baseline patient characteristics, we applied the eligibility criteria of CHAARTED (both high-volume [HV] and low-volume [LV] definition), STAMPEDE, and LATITUDE to determine the rate of men qualifying for treatment with A, D, or either of the two agents. Results: 98.0, 69.6, 28.4, and 47.1 percent of all 102 men fulfilled the STAMPEDE, CHAARTED-HV, CHAARTED-LV, and LATITUDE criteria, respectively. Considering that A funding for HNPC therapy is pending in Ontario, and that D funding is limited to men with CHAARTED-HV disease, the rate of D therapy was 62.0, 69.0, and 77.1 percent of patients conforming to STAMPEDE, CHAARTED-HV, and LATITUDE, respectively. 42 of 48 men (87.5%) conforming to LATITUDE would also be candidates for D, whereas 42 of 71 CHAARTED-HV patients (59.2%) would be eligible for A as alternative treatment. Hence, while all men fulfilling the STAMPEDE criteria (100 of 102, 98%) could be considered for either A or D, only 42 of 102 patients (41.2%) would be candidates for both of the drugs if the CHAARTED-HV and LATITUDE criteria were applied. Conclusions: In our patient population, applying the more restrictive CHAARTED-HV and LATITUDE criteria - as opposed to STAMPEDE - would result in around 30% or 50% fewer men offered D or A secondary to ADT, respectively. In addition, only around 40% of men would conform to both CHAARTED-HV and LATITUDE, and thus be candidates for both drugs.

scholarly journals Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial

2018 ◽  
Vol 36 (11) ◽  
pp. 1080-1087 ◽  
Author(s):  
Christos E. Kyriakopoulos ◽  
Yu-Hui Chen ◽  
Michael A. Carducci ◽  
Glenn Liu ◽  
David F. Jarrard ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Volume ◽  
Phase Iii ◽  
Cancer Trial ◽  
Term Survival ◽  
Chemohormonal Therapy ◽  
Androgen Ablation ◽  
Hormone Sensitive ◽  
Low Volume

Purpose Docetaxel added to androgen-deprivation therapy (ADT) significantly increases the longevity of some patients with metastatic hormone-sensitive prostate cancer. Herein, we present the outcomes of the CHAARTED (Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) trial with more mature follow-up and focus on tumor volume. Patients and Methods In this phase III study, 790 patients with metastatic hormone-sensitive prostate cancer were equally randomly assigned to receive either ADT in combination with docetaxel 75 mg/m2 for up to six cycles or ADT alone. The primary end point of the study was overall survival (OS). Additional analyses of the prospectively defined low- and high-volume disease subgroups were performed. High-volume disease was defined as presence of visceral metastases and/or ≥ four bone metastases with at least one outside of the vertebral column and pelvis. Results At a median follow-up of 53.7 months, the median OS was 57.6 months for the chemohormonal therapy arm versus 47.2 months for ADT alone (hazard ratio [HR], 0.72; 95% CI, 0.59 to 0.89; P = .0018). For patients with high-volume disease (n = 513), the median OS was 51.2 months with chemohormonal therapy versus 34.4 months with ADT alone (HR, 0.63; 95% CI, 0.50 to 0.79; P < .001). For those with low-volume disease (n = 277), no OS benefit was observed (HR, 1.04; 95% CI, 0.70 to 1.55; P = .86). Conclusion The clinical benefit from chemohormonal therapy in prolonging OS was confirmed for patients with high-volume disease; however, for patients with low-volume disease, no OS benefit was discerned.

scholarly journals American trends in expectant management utilization for prostate cancer from 2000 to 2009

2014 ◽  
Vol 8 (11-12) ◽  
pp. 775 ◽  
Author(s):  
Matthew J. Maurice ◽  
Robert Abouassaly ◽  
Hui Zhu
Keyword(s):  
Prostate Cancer ◽  
Expectant Management ◽  
Patient Characteristics ◽  
Veterans Affairs ◽  
Health Concern ◽  
Teaching Hospitals ◽  
Limited Life ◽  
Appreciable Increase ◽  
Low Volume

Introduction: The overtreatment of early prostate cancer has become a major public health concern. Expectant management (EM) is a strategy to minimize overtreatment, but little is known about its pattern of use. We sought to examine national EM utilization over the preceding decade.Methods: We examined prostate cancer treatment utilization from 2000 to 2009 using the National Cancer Database. EM use was analyzed in relation to other treatments and by cancer stage, age group, Charlson score, and hospital practice setting.Results: Overall, 109 997 (8.2%) men were managed initially with EM. EM usage remained stable at 7.6% to 9.5% from 2000 to 2009 with no appreciable increase for low-stage cancers. Usage was only slightly higher in elderly patients and in patients with multiple comorbidities. Veterans Affairs and low-volume hospitals had a much higher and increasing EM rate (range: 18.8%-29.8% and 15.1%-24.2%, respectively), compared to community hospitals, comprehensive cancer centres, and teaching hospitals, which showed no increased adoption. On further analysis, EM use remained high for low-stage cancers at Veterans Affairs and low-volume hospitals (24.0% and 19.1%, respectively), regardless of age or comorbidity, a pattern not shared by other practice settings.Conclusions: EM utilization remained low and stable last decade, regardless of disease or patient characteristics. Conversely, Veterans Affairs and low-volume hospitals led the trend in national EM adoption, particularly in men with low-stage cancers and limited life expectancies. The limitations of this dataset preclude any determination of the appropriateness of EM utilization. Nonetheless, further study is needed to identify factors influencing EM adoption to ensure its proper use in the future.

Multi-institutional evaluation of the clinical outcomes and genomic correlates of African Americans with metastatic castration-sensitive prostate cancer (mCSPC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 17-17
Author(s):  
Meredith MI Freeman ◽  
Ellen Jaeger ◽  
Jason Zhu ◽  
Audrey Phone ◽  
Roberto Nussenzveig ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Retrospective Analysis ◽  
Clinical Outcomes ◽  
De Novo ◽  
High Volume ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Treatment Intensification ◽  
Radium 223 ◽  
Incidence And Mortality

17 Background: Prostate cancer incidence and mortality is higher in African American (AA) as compared with non-AA men. The outcomes of mCSPC have significantly improved through treatment intensification yet, AA representation in those studies was suboptimal. We aimed to report the clinical, treatment outcomes and genomic data of AA men with mCSPC. Methods: Retrospective analysis of consecutive AA men with mCSPC at six Academic Institutions. The primary objective was to report the baseline characteristics and treatment patterns of mCSPC AA patients. The secondary objectives included the germline and somatic data and the clinical outcomes including PSA response, progression-free survival and subsequent treatments. Results: A total of 71 patients, median age 63 years (range, 41-84) with 58% Gleason 8-10, initial PSA of 69.8 ng/mL (0.02-7650), 59% with de-novo and 55% with high-volume (CHAARTED criteria; 20% visceral) disease, were included in this analysis. Twenty-two patients (31%) were treated with androgen deprivation therapy (ADT; 67% prior to year 2017), while 24%, 45% and 3% received docetaxel (median 6 cycles), abiraterone acetate and enzalutamide, respectively. Two patients received triplet therapy with ADT/docetaxel plus abiraterone or enzalutamide. Undetectable PSA was achieved in 35% after a median of 8.9 months (1.8-22.3). Among patients with mCSPC who received radiation therapy to prostate (n = 8), 89% had low volume disease. At time of cut off, thirty-two patients developed CRPC and the estimated median time to CRPC was 2.9 years (95% CI, 1.6-4.2). Subsequent therapies (n = 29) included abiraterone acetate (41%), enzalutamide (24%), bicalutamide (10%), radium-223 (7%), chemotherapy (7%), sipuleucel-T (3%) and others (7%). Five patients (8%) had pathogenic germline alterations (n = 2 BRCA1; n = 1 HOXB13, PALB2 and PMS2). Additionally, the most common somatic alterations among tested patients (n = 27) included CDK12, SPOP, TMPRSS2-ERG fusion, and TP53, all in 11% frequency. Of note, n = 2 BRCA1 and n = 1 high MSI/TMB. Conclusions: In one of the largest reported cohorts to our knowledge, mCSPC AA presented with a high number of de-novo and high-volume disease and might harbor a different germline and somatic genomic profile. The outcomes were comparable to contemporary phase III trials with treatment intensification, yet 31% were treated with ADT. Despite the known limitations associated with retrospective analysis, these data support prior observations where AA might have better initial PSA responses to ADT-based strategies compared with Caucasians, requiring further validation.

scholarly journals Inferences About Drug Safety in Phase III Trials in Oncology: Examples From Advanced Prostate Cancer

2020 ◽  
Author(s):  
Joshua Z Drago ◽  
Mithat Gönen ◽  
Gita Thanarajasingam ◽  
Chana A Sacks ◽  
Michael J Morris ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Drug Safety ◽  
Advanced Prostate Cancer ◽  
Patient Characteristics ◽  
Similar Efficacy ◽  
Phase Iii ◽  
Statistical Uncertainty ◽  
Cancer Disease ◽  
Disease States ◽  
Phase Iii Trials

Abstract Background Safety is a central consideration when choosing between multiple medications with similar efficacy. We aimed to evaluate whether adverse event (AE) profiles of 3 such drugs in advanced prostate cancer could be distinguished based on published literature. Methods We assessed consistency in AE reporting, AE risk in placebo arms, and methodology used for risk estimates and quantification of statistical uncertainty in randomized placebo-controlled phase III trials of apalutamide, enzalutamide, and darolutamide in advanced prostate cancer. Results Seven included clinical trials enrolled a total of 9215 participants (range = 1051-1715 per trial) across 3 prostate cancer disease states. Within disease states, baseline patient characteristics appeared similar between trials. Of 54 distinct AE types in total, only 3 (fatigue, hypertension, and seizure) were reported by all 7 trials. Absolute risks of AEs in the placebo arms differed systematically and more than twofold between trials, which was associated with visit frequency and resulted in different degrees of uncertainty in AE profiles between trials. No trial used inferential methodology to quantify statistical uncertainty in AE risks, but 6 of 7 trials drew overall conclusions. Two trials concluded that there was no elevated AE risk because of the intervention, including the trial of darolutamide, which had the greatest statistical uncertainty. Conclusions Rigorous comparison of drug safety was precluded by heterogeneity in AE reporting, variation in AE risks in the placebo arms, and lack of inferential statistical methodology, underscoring considerable opportunities to improve how AE data are collected, analyzed, and interpreted in oncology trials.

Novel therapies and emerging strategies for the treatment of patients with castration-resistant prostate cancer

2017 ◽  
Author(s):  
Deborah Mukherji ◽  
Aurelius Omlin ◽  
Carmel Pezaro ◽  
Johann De Bono
Keyword(s):  
Prostate Cancer ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Trial Participation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223 ◽  
New Treatments ◽  
Phase Iii Studies ◽  
Clinical And Translational Research

Castration-resistant prostate cancer (CRPC) represents a final stage of this malignancy for many men and is defined as the progression of prostate cancer despite castrate levels of testosterone. CRPC may present as a rising PSA, the development of new metastases, or worsening of known metastases. Recent advances have resulted in five new treatments for CRPC: the immunotherapy sipuleucel-T; the cytotoxic cabazitaxel; the androgen biosynthesis inhibitor abiraterone acetate; the radioisotope radium-223; and the antiandrogen enzalutamide. These have all improved overall survival in randomized phase III studies for patients with metastatic CRPC. Furthermore, multiple agents and combinations are currently in late-stage clinical testing. Men with advanced prostate cancer represent an important population for clinical and translational research and clinical trial participation should be considered as part of standard care.

scholarly journals Genomic Profiles of De Novo High- and Low-Volume Metastatic Prostate Cancer: Results From a 2-Stage Feasibility and Prevalence Study in the STAMPEDE Trial

2020 ◽  
pp. 882-897 ◽  
Author(s):  
Clare Gilson ◽  
Fiona Ingleby ◽  
Duncan C. Gilbert ◽  
Marina A. Parry ◽  
Nafisah B. Atako ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Chromatin Remodeling ◽  
Metastatic Prostate Cancer ◽  
De Novo ◽  
High Volume ◽  
Pi3k Pathway ◽  
Mismatch Repair Gene ◽  
Copy Number Loss ◽  
Hormone Sensitive ◽  
Low Volume

PURPOSE The STAMPEDE trial recruits men with newly diagnosed, high-risk, hormone-sensitive prostate cancer. To ascertain the feasibility of targeted next-generation sequencing (tNGS) and the prevalence of baseline genomic aberrations, we sequenced tumor and germline DNA from patients with metastatic prostate cancer (mPCa) starting long-term androgen-deprivation therapy (ADT). METHODS In a 2-stage approach, archival, formalin-fixed, paraffin-embedded (FFPE) prostate tumor core biopsy samples were retrospectively subjected to 2 tNGS assays. Prospective enrollment enabled validation using tNGS in tumor and germline DNA. RESULTS In stage 1, tNGS data were obtained from 185 tumors from 287 patients (65%); 98% had de novo mPCa. We observed PI3K pathway aberrations in 43%, due to PTEN copy-number loss (34%) and/or activating mutations in PIK3 genes or AKT (18%) and TP53 mutation or loss in 33%. No androgen receptor ( AR) aberrations were detected; RB1 loss was observed in < 1%. In stage 2, 93 (92%) of 101 FFPE tumors (biopsy obtained within 8 months) were successfully sequenced prospectively. The prevalence of DNA damage repair (DDR) deficiency was 14% (somatic) and 5% (germline). BRCA2 mutations and mismatch repair gene mutations were exclusive to high-volume disease. Aberrant DDR (22% v 15%), Wnt pathway (16% v 4%), and chromatin remodeling (16% v 8%) were all more common in high-volume compared with low-volume disease, but the small numbers limited statistical comparisons. CONCLUSION Prospective genomic characterization is feasible using residual diagnostic tumor samples and reveals that the genomic landscapes of de novo high-volume mPCa and advanced metastatic prostate cancer have notable similarities (PI3K pathway, DDR, Wnt, chromatin remodeling) and differences ( AR, RB1). These results will inform the design and conduct of biomarker-directed trials in men with metastatic hormone-sensitive prostate cancer.

Ineligibility of prostate cancer patients in the VA Connecticut Healthcare System (VACHS) to participate in clinical trials due to comorbidities

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5169-5169
Author(s):  
T. M. Mayer ◽  
W. K. Kelly ◽  
J. Concato ◽  
H. Chao
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Cancer Patients ◽  
Healthcare System ◽  
Patient Population ◽  
Performance Status ◽  
Phase Iii ◽  
Medical Conditions ◽  
Eligibility Criteria ◽  
Major Phase

5169 Background: A large proportion of prostate cancer patients receive their care within the VA Healthcare System. As this is a population affected by complex comorbidities, they may be underrepresented in oncology clinical trials. Our objective was to quantify the frequency with which castrate resistant prostate cancer (CRPC) patients in VACHS would be excluded from major phase III randomized controlled trials. Methods: We reviewed records of all prostate cancer patients at the VACHS between 2004–2007 and identified patients with CRPC. We reviewed eligibility criteria of 24 major phase III clinical trials, from 2006 onwards, studying investigational drugs for CRPC and created a “master list” (ML) of the most pertinent criteria. We analyzed our patient population according to both the ML criteria and to the TAX327 study criteria. Results: We identified 106 patients with CRPC, excluded 7 patients with insufficient medical records, and analyzed 99 patients. Performance status and life expectancy could not be accurately assessed from most charts and were excluded as specific criteria (though reflected in other serious medical condition). Major reasons for exclusion according to ML/TAX327 criteria include: 10/10 other malignancy within 5 years; 11/14 abnormal laboratory parameters; 27/30 other serious medical conditions; 3/4 abnormal cardiac function. ML list only exclusions: 5 active angina; 1 unstable DM; 1 major GI surgery; 1 contraindication to steroids. Serious medical conditions included: active cardiac disease, dementia, serious neurologic, psychiatric, vascular, pulmonary or hematologic disease, and poor performance status or compliance. Overall, 45% (45/99) of patients were excluded when using both the ML and TAX327 criteria. Conclusions: Approximately half of CRPC patients in the VACHS between 2004–2007 did not meet eligibility criteria for major therapeutic trials for CRPC. This retrospective review demonstrates that VA patients are underrepresented in randomized clinical trials for CRPC and are a special population due to their complex comorbidities. These findings underscore the importance of designing better clinical trials for CRPC with less barriers for this underrepresented but common patient population. No significant financial relationships to disclose.

Impact on overall survival (OS) with chemohormonal therapy versus hormonal therapy for hormone-sensitive newly metastatic prostate cancer (mPrCa): An ECOG-led phase III randomized trial.

2014 ◽  
Vol 32 (18_suppl) ◽  
pp. LBA2-LBA2 ◽  
Author(s):  
Christopher Sweeney ◽  
Yu-Hui Chen ◽  
Michael Anthony Carducci ◽  
Glenn Liu ◽  
David Frasier Jarrard ◽  
...  
Keyword(s):  
High Volume ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Chemohormonal Therapy ◽  
Visceral Metastases ◽  
Skeletal Related Events ◽  
Hormone Sensitive ◽  
Ecog Ps ◽  
Clinical Trial Information

LBA2 Background: Docetaxel (D) improves OS of men with mPrCa who have progressed on androgen deprivation therapy (ADT). We aimed to assess the benefit of upfront chemohormonal therapy for metastatic PrCa. Methods: 1:1 randomization to ADT alone or ADT + D dosed 75mg/m2 every 3 weeks for 6 cycles within 4 month (mos) of starting ADT. Stratification factors: high volume (HV) vs. low volume (LV) disease (HV: visceral metastases and/or 4 or more bone metastases); anti-androgen use beyond 30 days; Age ≥70 vs. < 70 years; ECOG PS 0-1 vs. 2; Prior adjuvant ADT > 12 vs. ≤ 12 mos; FDA approved drug for delaying skeletal related events. Key eligibility criteria: suitable organ and neurological function for D; adjuvant ADT ≤ 24 mos and no progression within 12 mos of adjuvant ADT. OS was the primary endpoint and the study was powered to assess for a 33.3% improvement in median OS (80% power and 1-sided alpha=2.5%). Projected median OS for ADT alone: HV-33 mos; LV-67 mos. Results: 790 men were accrued from 7/28/06 to 11/21/2012: ADT N=393; ADT + D: N=397; balanced for demographic, stratification and disease factors. Median age: 63 years (range: 36 to 91); 98% ECOG PS 0 or 1; 89% Caucasian; 24% prior radiotherapy, 24% prior prostatectomy; HV 64% on ADT and 67% on ADT + D. Data released after 4th interim analysis in Sept 2013 when O’Brien Fleming upper boundary was crossed with 53.1% information. This report reflects 1/16/2014 data with median follow-up of 29 mos with 137 deaths on ADT alone vs. 104 deaths on ADT+D. ADT+D: Grade (G) 3/4 Neutropenic fever: 4%/2%; G3 neuropathy: 1% sensory, 1% motor; 1 death due to treatment (no deaths due to treatment on ADT). Efficacy data is in the table below. After disease progression, 123 pts on ADT alone and 45 pts on ADT + D received docetaxel. Conclusions: ADT + D improves OS over ADT alone in men with HV mPrCa. Longer follow-up is needed for men with LV mPrCa. Clinical trial information: NCT00309985. [Table: see text]

Real-world experience with docetaxel for castration-sensitive prostate cancer from a population-based analysis.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 297-297 ◽  
Author(s):  
Jean-Michel Lavoie ◽  
Kevin Zou ◽  
Daniel Khalaf ◽  
Bernhard J. Eigl ◽  
Christian K. Kollmannsberger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
De Novo ◽  
Performance Status ◽  
Clinical Effectiveness ◽  
High Volume ◽  
Population Based ◽  
Phase Iii ◽  
Phase Iii Clinical Trials ◽  
Cancer Agency ◽  
Grade 3

297 Background: Phase III clinical trials have demonstrated efficacy with an overall survival (OS) benefit for the addition of docetaxel (DOC) to androgen deprivation therapy (ADT) for the treatment of metastatic castration-sensitive prostate cancer (mCSPC). The clinical effectiveness of DOC with ADT in the general patient population remains undefined. Methods: A population-based retrospective review was conducted of patients (pts) with mCSPC who received DOC at the BC Cancer Agency from 04/2015 to 02/2017. Patient and disease characteristics were extracted. Safety and clinical-effectiveness were evaluated. Results: 183 records were identified; 156 pts received DOC in the mCSPC setting. Baseline characteristics included a median age of 67 years (range 44-86) and visceral metastases (mets) present in 18%; 80% had high volume disease with 74% having > 3, and 54% > 10 bone mets; 76% had de-novo metastatic disease. All 6 planned DOC cycles were delivered in 126 cases (81%); it was stopped early for: toxicity in 15 (10%), unrelated death in 1 (0.6%), pt preference in 5 (3%) or disease progression in 9 (6%) cases. Dose reductions and delays were required in 61 (39%) and 25 (16%) cases, respectively. Grade 3-5 adverse events were noted in 62 (40%) cases, with 28 (18%) cases of febrile neutropenia (FN); there were no treatment-related deaths. Pts with FN had more bone mets (p = 0.046), but there was no difference in time from start of ADT to initiation of docetaxel, age, baseline performance status, PSA, or visceral involvement. PSA ≤ 0.2 ng/L was achieved in 41 (28%) cases after 6 months of ADT and maintained in 13 (8%) cases after 12 months. 41% of pts had developed CRPC within 1-yr, with a median time to CRPC of 14.3 months. Treatment for CRPC was given in 54 cases, with most pts receiving either abiraterone or enzalutamide (87%) with a PSA decline ≥50% occurring in 47%. Conclusions: Effectiveness of DOC with ADT in a general population of pts with mCSPC was associated with poorer outcomes and high rates of toxicity compared to the phase III studies. Response rates to first-line treatment for mCRPC with abiraterone or enzalutamide appear similar to those previously reported.

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