Overall adverse events in patients treated with abiraterone and enzalutamide for metastatic castration resistant prostate cancer: Meta-analysis of randomized clinical trials and real world reporting patterns from Eudra Vigilance

2019 ◽  
Vol 18 (9) ◽  
pp. e3260-e3262
Author(s):  
C. De Nunzio ◽  
G. Tema ◽  
R. Lombardo ◽  
A. Sica ◽  
A. Nacchia ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Adverse Events ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

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.

Neuropsychiatric adverse events of enzalutamide and abiraterone acetate: Meta-analysis of randomized clinical trials with real world reporting patterns from EudraVigilance.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 217-217 ◽  
Author(s):  
Maria Paola Moreno Perez ◽  
Miguel Sanchez Iznaola ◽  
Angela Garcia ◽  
Jacobo Muñoz del Toro ◽  
Joaquin Casariego ◽  
...  
Keyword(s):  
Real World ◽  
Randomized Clinical Trials ◽  
Proportional Reporting Ratio ◽  
Meta Analysis ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Increased Risk ◽  
Neuropsychiatric Adverse Effects ◽  
Reporting Pattern

217 Background: Androgen deprivation is associated with cognitive decline and mood changes. Abiraterone acetate plus prednisone (AAP) and enzalutamide (ENZ) are oral hormonal agents for the treatment of metastatic castration resistant prostate cancer (mCPRC); both target the androgen signaling pathway. Meta-analysis for individual neuropsychiatric adverse effects (NAEs) associated with these drugs has not been available in the literature. Methods: Following the methodology presented by Ruiz et al. a further meta-analysis was performed to estimate the pooled Relative Risk (RR) of NAEs for AAP and ENZ. A complementary analysis of the EudraVigilance database was performed to explore the consistency of the real world adverse drug reactions (ADR) reporting pattern with the meta-analysis. Results: The meta-analysis results indicate that patients treated with ENZ had a statistically significant higher risk of restless leg syndrome (RLS), anxiety, headache and insomnia vs control. Both AAP and ENZ showed significant increased risk for falls vs control. The Proportional Reporting Ratio (PRR) of ADRs reported in Eudra is higher with ENZ than with AAP for all the variables analyzed. Conclusions: NAEs studied are more prevalent with ENZ vs placebo than AAP vs prednisone plus placebo. Reporting trend in Eudra is consistent with this results. [Table: see text]

scholarly journals Real-world safety profile of abiraterone acetate in patients with castration-resistant prostate cancer and cardiovascular comorbidities: a retrospective, single center study

2017 ◽  
Vol 5 (3) ◽  
pp. 20-24
Author(s):  
Giovanni Fuca ◽  
Elena Verzoni ◽  
Alessia Mennitto ◽  
Michele Prisciandaro ◽  
Raffaele Ratta ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Real World ◽  
Safety Profile ◽  
Abiraterone Acetate ◽  
Left Ventricular ◽  
Cardiovascular Safety ◽  
Castration Resistant Prostate Cancer ◽  
Cardiovascular Comorbidities ◽  
Castration Resistant

Background: Abiraterone acetate became a referral treatment for metastatic castration-resistant prostate cancer (mCRPC) in a post-docetaxel setting despite a remarkable percentage of cardiovascular adverse events (AEs). As a consequence, the evaluation of cardiovascular safety in patients at risk should be mandatory. We aimed to assess the cardiovascular safety of abiraterone acetate in a real-world series of mCRPC patients treated at our institution. Materials and Methods: We retrospectively included mCRPC patients with at least 1 active cardiovascular comorbidity or risk factor according to the European Society of Cardiology (ESC) guidelines and who started treatment with abiraterone acetate from April 2011 to July 2012. Cardiac assessment with electrocardiogram and echocardiogram was performed at baseline and at treatment discontinuation. AEs were defined according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Statistical analyses were performed by descriptive statistics as appropriate. Results: We included 51 patients of whom 18% had an ESC score risk for a major cardiovascular event ≥4%. At a median follow-up of 36 months, no cardiac AEs (rhythm abnormalities or left ventricular function decrease) were observed. The most frequent grade 1-2 AE reported was fluid retention (18%) followed by hypertension and asthenia (16%). The most frequent grade 3-4 AEs were asthenia and pruritus/rash. No patients discontinued abiraterone because of toxicity. Conclusions: Abiraterone acetate showed a favorable safety profile in mCRPC patients with cardiovascular comorbidities or risk factors in a post-docetaxel setting, but further studies are needed to confirm our findings and to explore other settings of disease.

scholarly journals A DREAM Challenge to Build Prediction Models for Short-Term Discontinuation of Docetaxel in Metastatic Castration-Resistant Prostate Cancer

2017 ◽  
pp. 1-15 ◽  
Author(s):  
Fatemeh Seyednasrollah ◽  
Devin C. Koestler ◽  
Tao Wang ◽  
Stephen R. Piccolo ◽  
Roberto Vega ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Clinical Trials ◽  
High Risk ◽  
Adverse Events ◽  
Clinical Features ◽  
Prediction Models ◽  
Castration Resistant Prostate Cancer ◽  
Early Discontinuation ◽  
Castration Resistant

Purpose Docetaxel has a demonstrated survival benefit for patients with metastatic castration-resistant prostate cancer (mCRPC); however, 10% to 20% of patients discontinue docetaxel prematurely because of toxicity-induced adverse events, and the management of risk factors for toxicity remains a challenge. Patients and Methods The comparator arms of four phase III clinical trials in first-line mCRPC were collected, annotated, and compiled, with a total of 2,070 patients. Early discontinuation was defined as treatment stoppage within 3 months as a result of adverse treatment effects; 10% of patients discontinued treatment. We designed an open-data, crowd-sourced DREAM Challenge for developing models with which to predict early discontinuation of docetaxel treatment. Clinical features for all four trials and outcomes for three of the four trials were made publicly available, with the outcomes of the fourth trial held back for unbiased model evaluation. Challenge participants from around the world trained models and submitted their predictions. Area under the precision-recall curve was the primary metric used for performance assessment. Results In total, 34 separate teams submitted predictions. Seven models with statistically similar area under precision-recall curves (Bayes factor ≤ 3) outperformed all other models. A postchallenge analysis of risk prediction using these seven models revealed three patient subgroups: high risk, low risk, or discordant risk. Early discontinuation events were two times higher in the high-risk subgroup compared with the low-risk subgroup. Simulation studies demonstrated that use of patient discontinuation prediction models could reduce patient enrollment in clinical trials without the loss of statistical power. Conclusion This work represents a successful collaboration between 34 international teams that leveraged open clinical trial data. Our results demonstrate that routinely collected clinical features can be used to identify patients with mCRPC who are likely to discontinue treatment because of adverse events and establishes a robust benchmark with implications for clinical trial design.

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