scholarly journals Real-World Utilization of Androgen Deprivation Therapy-Intensification Among Older Canadian Men with de Novo Metastatic Prostate Cancer

2021 ◽  
Author(s):  
Christopher J D Wallis ◽  
Shawn Malone ◽  
Ilias Cagiannos ◽  
Scott C Morgan ◽  
Robert J Hamilton ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Real World ◽  
De Novo ◽  
Population Based ◽  
P Uptake ◽  
Abiraterone Acetate ◽  
Androgen Deprivation ◽  
Treatment Intensification ◽  
Clinical Trial Evidence

Abstract Background Despite the wealth of evidence demonstrating the efficacy of treatment intensification beyond androgen deprivation therapy (ADT) among patients with de novo metastatic castration-sensitive prostate cancer (mCSPC), little is known of its real-world utilization. This study examined the real-world uptake of ADT treatment intensification among older men in a large Canadian province. Methods We performed a retrospective population-based cohort study using province-wide linked administrative data in Ontario, Canada. Patients 66 years and older with de novo mCSPC were included and their treatment with conventional ADT-based regimens, ADT plus next-generation androgen receptor-axis-targeted therapy (ARAT), and ADT plus docetaxel were identified and stratified by time. Results From 2014 to 2019, 3556 patients were identified with de novo mCSPC. Most patients (n = 2794, 78.6%) were treated with a conventional ADT regimen while 399 (11.2%) patients received ADT intensification with docetaxel and 52 (1.5%) patients received abiraterone acetate plus prednisone (AA+P). In a time-stratified analysis of ADT intensification before and after the pivotal AA+P trial (LATITUDE), AA+P uptake increased from 0.5% to 3.0% while docetaxel use dropped from 12.0% to 10.0%. The median survival of the study population was 18 months (IQR = 10–31). Conclusion The majority of patients with de novo mCSPC are treated with ADT alone in the Canadian real-world setting, despite randomized clinical trial evidence of benefit with the use of ADT-intensified regimens. As ADT treatment intensification is substantially under-used, better understanding the barriers to treatment and targeted education to address these are needed.

Use and outcomes in men with metastatic castration-sensitive prostate cancer (mCSPC) treated with docetaxel in addition to androgen deprivation therapy (ADT): Analysis of real-world data in the United States (US).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19322-e19322
Author(s):  
Neeraj Agarwal ◽  
Suneel Mundle ◽  
Lindsay Dearden ◽  
Ravi C. Potluri ◽  
Sandhya Nair ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Real World ◽  
De Novo ◽  
Specific Antigen ◽  
The United States ◽  
Androgen Deprivation ◽  
Castration Resistant Prostate Cancer ◽  
The Real ◽  
The Us

e19322 Background: mCSPC patients treated with docetaxel + androgen deprivation therapy (D+ADT) demonstrate increased overall survival (OS)1,2. However, limited real-world outcome data is available for such patients. This study assesses the real-world use and outcomes with D+ADT in mCSPC in the US. Methods: Adult (≥18 years old) men with mCSPC (defined as men with metastasis at index diagnosis of prostate cancer [de novo] or those who progressed to mCSPC after prior diagnosis of localized disease) were retrospectively identified from the Optum (2007–2018) and SEER Medicare (2007–2016) databases. Men diagnosed with mCSPC in or after 2014 with exposure to docetaxel and no brain metastasis were included for analysis. Patients were characterized based on age; baseline prostate specific antigen (PSA) level; administration of ADT; prior radiotherapy (RT); prior radical prostatectomy (RP); presence of visceral disease, bone or bone + visceral metastases; and treatment duration of docetaxel. OS and time to metastatic castration-resistant prostate cancer (mCRPC) were measured. Results: Among 4959 men identified with mCSPC during or after 2014, 192 (3.8%) received D+ADT ± Bicalutamide as first line systemic therapy. Baseline characteristics are presented in the Table below. Mean ± SD duration of docetaxel exposure was 115 ± 84.2 days (median 118 days). Median OS among these men was 30.5 (28.1, 36.7) months and median time to mCRPC was 18.3 (14.5, 24.6) months. Only 9% of men received docetaxel for ≥6 cycles (180 days); median OS in these men was NR (19.1- NR) with 74% surviving at 2 years compared to 65% surviving at 2 years in those with docetaxel duration <6 cycles. Conclusions: Use of docetaxel in the real-world mCSPC patient population in the US is limited. Majority of men received less than the recommended dose of 6 cycles. OS with D+ADT in real-world patients with mCSPC appears to be lower than the OS reported in published trials. References:1) Sweeney CJ, et al. N Engl J Med. 2015;373:737–46. 2) James ND, et al. Lancet. 2016;387:1163–77. Funding: Janssen Research & Development, LLC. [Table: see text]

scholarly journals Radiation therapy dose and androgen deprivation therapy in localized prostate cancer: a meta-regression of 5-year outcomes in phase III randomized controlled trials

2021 ◽  
Author(s):  
Tommy Jiang ◽  
Daniela Markovic ◽  
Jay Patel ◽  
Jesus E. Juarez ◽  
Ting Martin Ma ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Androgen Deprivation Therapy ◽  
Dose Escalation ◽  
Low Dose ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
Localized Prostate Cancer ◽  
Treatment Intensification ◽  
Meta Regression

Abstract Background While multiple randomized trials have evaluated the benefit of radiation therapy (RT) dose escalation and the use and prolongation of androgen deprivation therapy (ADT) in the treatment of prostate cancer, few studies have evaluated the relative benefit of either form of treatment intensification with each other. Many trials have included treatment strategies that incorporate either high or low dose RT, or short-term or long-term ADT (STADT or LTADT), in one or more trial arms. We sought to compare different forms of treatment intensification of RT in the context of localized prostate cancer. Methods Using preferred reporting items for systemic reviews and meta-analyses (PRISMA) guidelines, we collected over 40 phases III clinical trials comparing different forms of RT for localized prostate cancer. We performed a meta-regression of 40 individual trials with 21,429 total patients to allow a comparison of the rates and cumulative proportions of 5-year overall survival (OS), prostate cancer-specific mortality (PCSM), and distant metastasis (DM) for each treatment arm of every trial. Results Dose-escalation either in the absence or presence of STADT failed to significantly improve any 5-year outcome. In contrast, adding LTADT to low dose RT significantly improved 5-year PCSM (Odds ratio [OR] 0.34, 95% confidence interval [CI] 0.22–0.54, p < 0.001) and DM (OR 0.35, 95% CI 0.20–0.63. p < 0.001) over low dose RT alone. Adding STADT also significantly improved 5-year PCSM over low dose RT alone (OR 0.55, 95% CI 0.41–0.75, p < 0.001). Conclusion While limited by between-study heterogeneity and a lack of individual patient data, this meta-analysis suggests that adding ADT, versus increasing RT dose alone, offers a more consistent improvement in clinical endpoints.

Management of Metastatic Castrate-sensitive Prostate Cancer

2018 ◽  
Author(s):  
Derya Tilki ◽  
Marc A Dall’era ◽  
Christopher P Evans
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Survival Benefit ◽  
Metastatic Prostate Cancer ◽  
Oncologic Outcome ◽  
Standard Of Care ◽  
Abiraterone Acetate ◽  
Androgen Deprivation ◽  
Newly Diagnosed ◽  
Treatment Paradigm

Oncologic outcome of patients with newly diagnosed metastatic prostate cancer (mPCa) is poor. The treatment paradigm for newly diagnosed mPCa has changed. The standard of care for men with metastatic hormone-naive prostate cancer has been systemic androgen deprivation therapy (ADT). Previous randomized studies demonstrated an overall survival benefit by the addition of early chemotherapy with six cycles of docetaxel. More recently, results from randomized trials also demonstrated a survival benefit by the addition of abiraterone acetate to the ADT in men with metastatic disease. The aim of this review is to summarize the results from most recent studies, including men with newly diagnosed metastatic hormone-naive prostate cancer, focusing on chemotherapy and ADT. This review contains 1 figure, 2 tables, and 47 references.  Key Words: abiraterone acetate, androgen deprivation therapy, androgen deprivation, castrate sensitive, chemotherapy, continuous androgen deprivation, docetaxel, hormone-naive, intermittent androgen deprivation, metastatic prostate cancer

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.

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