scholarly journals Abiraterone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: a systematic review of ‘real-life’ studies

2018 ◽  
Vol 10 (10) ◽  
pp. 305-315 ◽  
Author(s):  
Michele Marchioni ◽  
Petros Sountoulides ◽  
Maida Bada ◽  
Sebastiano Rapisarda ◽  
Cosimo De Nunzio ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Meta Analysis ◽  
Real Life ◽  
Castration Resistant Prostate Cancer ◽  
The Real ◽  
Castration Resistant ◽  
Real Life Setting ◽  
Grade 3 ◽  
Baseline Psa

Background: To assess the efficacy and safety of treatment with abiraterone acetate (AA) in chemotherapy-naïve men with metastatic castration-resistant prostate cancer (mCRPC) in the ‘real-life’ setting. Methods: Data acquisition on the outcomes of the use of AA in chemotherapy-naive patients with mCRPC was performed by a MEDLINE comprehensive systematic literature search using combinations of the following key words: ‘prostate cancer’, ‘metastatic’, ‘castration resistant’, ‘abiraterone’, ‘real life’, and excluding controlled clinical trials (phase II and III studies). Identification and selection of the studies was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria. Outcomes of interest were overall survival (OS), progression-free survival (PFS), 12-week 50% reduction in prostate-specific antigen (PSA), and grade 3 and higher adverse events. Data were narratively synthesized in light of methodological and clinical heterogeneity. Results: Within the eight identified studies that fulfilled the criteria, a total of 801 patients were included in the meta-analysis. Baseline PSA ranged between 9.5 and 212.0 ng/ml. Most of the patients had bone metastases. Duration of treatment with AA was longer in the studies with lower baseline PSA levels. The median OS ranged between 14 and 36.4 months. The PFS, assessed according to different definitions, ranged from 3.9 to 18.5 months. A 50% PSA reduction at 12 weeks was reached by a variable percentage of patients ranging from 36.0% to 62.1%. Finally, the rate of grade 3 and higher adverse events was reported in three studies and ranged from 4.4% to 15.5%. Conclusions: Despite the high grade of heterogeneity among studies, treatment with AA seems to ensure good survival outcomes in the ‘real-life’ setting. However, prospective studies based on patients’ characteristics being more similar to ‘real-life’ patients are necessary.

scholarly journals Overall and progression-free survival with cabazitaxel in metastatic castration-resistant prostate cancer in routine clinical practice: the FUJI cohort

2019 ◽  
Vol 121 (12) ◽  
pp. 1001-1008 ◽  
Author(s):  
Magali Rouyer ◽  
◽  
Stéphane Oudard ◽  
Florence Joly ◽  
Karim Fizazi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Real Life ◽  
Progression Free Survival ◽  
European Medicines Agency ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Grade 3 ◽  
Metastatic Sites

Abstract Background Cabazitaxel is a treatment of metastatic castration-resistant prostate cancer (mCRPC) after docetaxel failure. The FUJI cohort aimed to confirm the real-life overall and progression-free survival (OS, PFS) and safety of cabazitaxel. Methods Multicentre, non-interventional cohort of French mCRPC patients initiating cabazitaxel between 2013 and 2015, followed 18 months. Results Four hundred one patients were recruited in 42 centres. At inclusion, median age was 70, main metastatic sites were bones (87%), lymph nodes (42%) and visceral (20%). 18% had cabazitaxel in 2nd-line treatment, 39% in 3rd-line and 43% in 4th-line or beyond. All had prior docetaxel, and 82% prior abiraterone, enzalutamide or both. Median duration of cabazitaxel treatment was 3.4 months. Median OS from cabazitaxel initiation was 11.9 months [95% CI: 10.1–12.9]. In multivariate analyses, grade ≥ 3 adverse events, visceral metastases, polymedication, and >5 bone metastases were associated with a shorter OS. Main grade ≥ 3 adverse events were haematological with 8% febrile neutropenia. Conclusion Real-life survival with cabazitaxel in FUJI was shorter than in TROPIC (pivotal trial, median OS 15.1 months) or PROSELICA (clinical trial 20 vs 25 mg/m2, median OS, respectively, 13.4 and 14.5 months). There was no effect of treatment-line on survival. No unexpected adverse concerns were identified. Study registration It was registered with the European Medicines Agency EUPASS registry, available at www.encepp.eu, as EUPAS10391. It has been approved as an ENCEPP SEAL study.

Survival outcome in patients with metastatic castration-resistant prostate cancer according to first-line treatment.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5570-5570
Author(s):  
Marine Gross-Goupil ◽  
Nicolas H. Thurin ◽  
Magali Rouyer ◽  
Jérémy Jové ◽  
Thibaud Haaser ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Real Life ◽  
Abiraterone Acetate ◽  
Line Treatment ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Free Survival ◽  
Castration Resistant ◽  
Real Life Setting ◽  
First Line Treatment

5570 Background: Therapeutic strategy in metastatic castration-resistant prostate cancer (mCRPC) has evolved significantly with the introduction of abiraterone acetate in association with prednisone/prednisolone in first-line treatment in December 2012. This work aimed to compare the effectiveness of abiraterone acetate and docetaxel as first-line treatments for mCRPC, in real-life setting. Methods: Patients with mCRPC were identified in the main scheme of the National Healthcare System database (SNDS), which covers about 86% of the French population, and capturing all reimbursed healthcare expenditures and hospital discharge summaries. Those initiating docetaxel or abiraterone acetate in 1st line in 2014 were included and 1:1 matched on the previous prostate cancer stage before mCRPC status, the delay from the date of initial diagnosis and a high-dimensional propensity score. The 36-month overall survival and the 36-month discontinuation-free survival (i.e. survival time until treatment switch or death) were compared using Cox proportional hazards risk model. Results: In 2014, out of the 12,951 patients with prevalent mCRPC, 1,214 initiated docetaxel in 1st line and 2 444 initiated abiraterone. A total of 716 patients per group were matched with good comparability (C-statistic = 0.6). The median duration of docetaxel–defined as the time between the first and the last infusion–was 7.3 months with a median of 6 infusions. The median duration of abiraterone acetate–corresponding to the period covered by the dispensed drug–was 9.1 months. Near 70% of the docetaxel and 62% of the abiraterone acetate patients received a 2nd line of treatment. Results related to the main survival outcomes are presented in the table below. Conclusions: First-line treatment with abiraterone acetate in mCRPC patients results in a better 36-month overall survival and discontinuation-free survival compared to docetaxel in real-life setting. [Table: see text]

scholarly journals Sipuleucel-T and Androgen Receptor-Directed Therapy for Castration-Resistant Prostate Cancer: A Meta-Analysis

2016 ◽  
Vol 2016 ◽  
pp. 1-10
Author(s):  
Renliang Yi ◽  
Baoxin Chen ◽  
Peng Duan ◽  
Chanjiao Zheng ◽  
Huanyu Shen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Adverse Event ◽  
Placebo Group ◽  
Treatment Group ◽  
Meta Analysis ◽  
Castration Resistant Prostate Cancer ◽  
Time To Progression ◽  
Castration Resistant ◽  
Grade 3

New treatments, such as sipuleucel-T and androgen receptor- (AR-) directed therapies (enzalutamide (Enz) and abiraterone acetate (AA)), have emerged and been approved for the management of castration-resistant prostate cancer (CRPC). There are still debates over their efficacy and clinical benefits. This meta-analysis aimed to investigate the efficacy and safety of sipuleucel-T and AR-directed therapies in patients with CRPC. RevMan 5.1 was used for pooled analysis and analysis of publication bias. Seven studies were included in the meta-analysis, with three studies in sipuleucel-T (totally 737 patients, 488 patients in treatment group, and 249 patients in placebo group) and four in AR-directed therapies (totally 5,199 patients, 3,015 patients in treatment group, and 2,184 patients in placebo group). Treatment with sipuleucel-T significantly improved overall survival in patients with CRPC and was not associated with increased risk of adverse event of grade ≥3 (p>0.05). However, treatment with sipuleucel-T did not improve time-to-progression and reduction of prostate-specific antigen (PSA) level ≥50% was not significantly different from that with placebo. AR-directed therapies significantly improved overall survival in patients with CRPC and improved time-to-progression and reduction of PSA level ≥50%. AR-directed therapies did not increase risk of adverse event of grade ≥3 (p>0.05).

scholarly journals Overall survival and adverse events after treatment with darolutamide vs. apalutamide vs. enzalutamide for high-risk non-metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis

2021 ◽  
Author(s):  
Mike Wenzel ◽  
Luigi Nocera ◽  
Claudia Collà Ruvolo ◽  
Christoph Würnschimmel ◽  
Zhe Tian ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
High Risk ◽  
Meta Analysis ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Pubmed Search ◽  
Grade 3 ◽  
Meta Analyses

Abstract Background The most recent overall survival (OS) and adverse event (AE) data have not been compared for the three guideline-recommended high-risk non-metastatic castration-resistant prostate cancer (nmCRPC) treatment alternatives. Methods We performed a systematic review and network meta-analysis focusing on OS and AE according to the most recent apalutamide, enzalutamide, and darolutamide reports. We systematically examined and compared apalutamide vs. enzalutamide vs. darolutamide efficacy and toxicity, relative to ADT according to PRISMA. We relied on PubMed search for most recent reports addressing prospective randomized trials with proven predefined OS benefit, relative to ADT: SPARTAN, PROSPER, and ARAMIS. OS represented the primary outcome and AEs represented secondary outcomes. Results Overall, data originated from 4117 observations made within the three trials that were analyzed. Regarding OS benefit relative to ADT, darolutamide ranked first, followed by enzalutamide and apalutamide, in that order. In the subgroup of PSA-doubling time (PSA-DT) ≤ 6 months patients, enzalutamide ranked first, followed by darolutamide and apalutamide in that order. Conversely, in the subgroup of PSA-DT 6–10 months patients, darolutamide ranked first, followed by apalutamide and enzalutamide, in that order. Regarding grade 3+ AEs, darolutamide was most favorable, followed by enzalutamide and apalutamide, in that order. Conclusion The current network meta-analysis suggests the highest OS efficacy and lowest grade 3+ toxicity for darolutamide. However, in the PSA-DT ≤ 6 months subgroup, the highest efficacy was recorded for enzalutamide. It is noteworthy that study design, study population, and follow-up duration represent some of the potentially critical differences that distinguish between the three studies and remained statistically unaccounted for using the network meta-analysis methodology. Those differences should be strongly considered in the interpretation of the current and any network meta-analyses.

Relative risk of HTN and major cardiovascular events associated with use of androgen receptor antagonists for nonmetastatic, castration-resistant prostate cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17605-e17605
Author(s):  
Nusrat Jahan ◽  
Francis Mogollon-Duffo ◽  
Shabnam Rehman ◽  
Sakshi Singal ◽  
Fred L. Hardwicke
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Relative Risk ◽  
Meta Analysis ◽  
Castration Resistant Prostate Cancer ◽  
Phase 3 ◽  
Castration Resistant ◽  
Increased Risk ◽  
Myocardial Infraction ◽  
Grade 3

e17605 Background: Metastatic, castration-resistant prostate cancer (mCRPC) is a lethal disease, often preceded by nonmetastatic, castration-resistant phase. Recently, three androgen receptor (AR) antagonists — apalutamide, enzalutamide, and darolutamide — have been approved for nonmetastatic, castration-resistant prostate cancer (nmCRPC). AR-antagonists have been associated with increased risk of hypertension (HTN) and major cardiovascular (CV) events. We conducted a systematic review and meta-analysis of the published phase 3 randomized controlled trials (RCTs) to determine the relative risk of HTN and major CV events associated with use of AR-antagonists for nmCRPC. Methods: We conducted a systematic search at PUBMED, MEDLINE, EMBASE, and meeting abstracts from inception until November 2019. Published phase 3 RCTs using AR-antagonists in the study arm for nmCRPC and reporting the number of events of HTN and major CV events were included in the analyses. We used Mantel-Haenszel (MH) method and random effects model to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was tested with I2 value and Cochran’s Q-test. Results: Three phase 3 RCTs (ARAMIS, PROSPER, and SPARTAN) randomizing 2687 patients in the AR-antagonist arms and 1417 patients in the control arms were included in the final analysis for HTN. SPARTAN did not include data for major CV events; hence, other two studies comprising 2903 patients were analyzed for major CV events. Major CV events included myocardial infraction/coronary artery disease, ischemic/hemorrhagic cerebrovascular events, and heart failure. AR-antagonists used in the study arms were — ARAMIS: darolutamide, PROSPER: enzalutamide, and SPARTAN: apalutamide. Placebo was used in the control arms. All patients continued androgen deprivation therapy. Randomization was 2:1 in all studies. The pooled RR of any-grade HTN is 1.5 (95% CI: 1.03 – 2.18, p = 0.03, I2 = 70%); and, the pooled RR of grade ≥3 HTN is 1.39 (95% CI: 1.03 – 1.88, p = 0.03, I2 = 13%). The pooled RR of any-grade major CV events is 1.49 (95% CI: 1.05 – 2.13, p = 0.03, I2 = 0%); and, the pooled RR of grade ≥3 major CV events is 1.80 (95% CI: 1.11 – 2.92, p = 0.02, I2 = 0%). Conclusions: Our meta-analysis demonstrated use of AR-antagonists for nmCRPC is associated with increased risk of HTN and major CV events. A careful selection of patients and aggressive management of the CV risk factors are crucial to enhance safety and proper utilization of these promising drugs.

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