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 Efficacy and Safety of Abiraterone Acetate and Enzalutamide for the Treatment of Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
ZhenHeng Wei ◽  
ChuXin Chen ◽  
BoWen Li ◽  
YongYue Li ◽  
Hong Gu
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Prostate Specific Antigen ◽  
Meta Analysis ◽  
Specific Antigen ◽  
Abiraterone Acetate ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
Randomized Controlled ◽  
Castration Resistant

ObjectiveThe androgen receptor-targeting drugs abiraterone acetate and enzalutamide have shown positive results as treatments for metastatic castration-resistant prostate cancer (mCRPC). Therefore, a meta-analysis was conducted to compare the efficacy and safety of abiraterone acetate and enzalutamide in patients with mCRPC.MethodsWe retrieved relevant articles from PubMed, Cochrane, and EMBASE published before December 31, 2020. Eleven articles were initially selected, and four phase III, double-blind, randomized controlled trials of abiraterone acetate and enzalutamide that involved 5199 patients with mCRPC were included. The end points were time to prostate-specific antigen progression (TTPP), according to the prostate-specific antigen working group criteria; overall survival (OS); and radiographic progression-free survival (rPFS).ResultsFour randomized, controlled clinical trials involving 5199 patients were included in this study. The results of the meta-analysis showed that compared with placebo alone, abiraterone significantly improved OS (HR=0.69, 95% CI: 0.60-0.8, P<0.00001), rPFS (HR=0.64, 95% CI: 0.57-0.71, P < 0.00001), and TTPP (HR=0.52, 95% CI: 0.45-0.59, P < 0.00001) in patients with mCRPC. Compared with placebo, enzalutamide significantly improved OS (HR=0.67, 95% CI: 0.59-0.75, P<0.00001), rPFS (HR=0.33, 95% CI: 0.29-0.37, P< 0.00001), and TTPP (HR=0.19, 95% CI: 0.17-0.22, P < 0.00001). An indirect comparison was performed to compare the efficacy of abiraterone and enzalutamide. The results showed that there was no significant difference between abiraterone and enzalutamide with regard to improving the OS of patients with mCRPC (HR=1.03, 95% CI: 0.854-1.242). Enzalutamide was superior to abiraterone with regard to improving rPFS in patients with mCRPC (HR=0.516, 95% CI: 0.438-0.608). With regard to improving TTPP, the efficacy of enzalutamide was better than that of abiraterone (HR=0.365, 95% CI: 0.303-0.441). In sAE, there was no difference between abiraterone and enzalutamide (P=0.21, I2 = 38%).ConclusionsCompared with placebo, both abiraterone and enzalutamide significantly prolonged OS, rPFS, and TTPP in patients with mCRPC. There was no difference in safety between abiraterone and enzalutamide. In addition, enzalutamide had better efficacy than abiraterone with regard to improving rPFS and TTPP but not OS, but the level of evidence was low. Therefore, a large direct comparison trial is needed to compare the efficacy of the two drugs.Systematic Review RegistrationPROSPERO, identifier (CRD42021226808)

Treatment patterns of new metastatic castration-resistant prostate cancer (mCRPC) therapies: Real-world evidence from three datasets.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 228-228 ◽  
Author(s):  
Lorie Ellis ◽  
Marie-Helene Lafeuille ◽  
Laurence Gozalo ◽  
Patrick Lefebvre ◽  
Elisabetta Malangone-Monaco ◽  
...  
Keyword(s):  
Real World ◽  
Single Agent ◽  
Study Drug ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Treatment Interventions ◽  
Castration Resistant ◽  
Community Oncology ◽  
Real World Evidence ◽  
Line Of Therapy

228 Background: Little information exists regarding the sequences in which new mCRPC therapies with evidence of survival benefits are used. This study aims at describing the sequence of mCRPC medication use as observed in 3 healthcare datasets. Methods: Healthcare claims datasets (Dataset #1 and #2) and a community oncology electronic medical record (Dataset #3) were used to identify PC patients with ≥ 1 claim for a study drug (abiraterone acetate--AA, cabazitaxel--CAB, docetaxel – DOC, enzalutamide – ENZ, and sipuleucel T – SIP) occurring after 9/1/2012. The index date was the 1st study drug claim. Patients were excluded if a study drug claim occurred prior to 9/1/2012. Descriptive statistics summarized the proportion of patients receiving one vs. two or more lines of therapy. The prevalence of 1st line therapy and of 1st to 2nd-line sequences was analyzed. Results: Analysis of 3 unique datasets with > 5,900 PC patients revealed most patients received a single line of therapy. AA and DOC were the most common 1st line agents. The five most-prevalent 1st- to 2nd-line sequences identified in each database are shown in the table below. The most commonly observed 1st- to 2nd-line sequences were AA-ENZ, AA-DOC, and DOC-AA. Conclusions: Real world treatment selection for 5 mCRPC medications was consistent across 3 datasets. The majority of PC patients had a prescription/claim for a single agent. AA and DOC were the most commonly selected 1st line treatments. A 2nd-line agent was observed in 14-33% of patients. Similar patterns of 1st-2nd line sequences were observed between datasets. Further research is warranted with longer follow-up and consideration of other treatment interventions. [Table: see text]

Incidence of skeletal-related events in men with castration-resistant prostate cancer.

2018 ◽  
Vol 36 (34_suppl) ◽  
pp. 188-188
Author(s):  
Alison Tse Kawai ◽  
David Martinez ◽  
Catherine W. Saltus ◽  
Zdravko Vassilev ◽  
Montse Soriano-Gabarro ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Real World ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Cohort Entry ◽  
Risk Of Death ◽  
Castration Resistant ◽  
Increased Risk ◽  
Before And After ◽  
Skeletal Related Events

188 Background: Skeletal-related events (SREs) are common in men with bone metastases and have negative consequences for patients with castration-resistant prostate cancer (CRPC), including pain, reduced quality of life, and increased risk of death. Published data on background rates of SREs in men with CPRC in real-world practice are sparse. Methods: We included men aged ≥ 65 years in the SEER-Medicare database with a prostate cancer diagnosis in 2000-2011 if they had no prior malignancy, had surgical or medical castration, and met protocol-defined criteria for castration resistance. Castration resistance was inferred from subsequent treatment with any of these systemic therapies: abiraterone, cabazitaxel, docetaxel, enzalutamide, mitoxantrone, or sipuleucel-T. The first occurrence of an SRE was identified in Medicare claims using diagnosis or procedure codes for fracture, bone surgery, radiation therapy, or spinal cord compression. We estimated incidence rates (IRs) of SREs in all eligible person-time and stratified by person-time before and after any use of the following bone-targeted agents (BTAs): alendronate, denosumab, ibandronate, pamidronate, risedronate, or zoledronic acid. Results: Of 2,234 men with CRPC (84% white, mean age 76.6 years), 896 (40%) had an SRE during follow-up, with 74% occurring within a year after cohort entry. Overall, the IR of SREs was 3.78 (95% CI, 3.53-4.03) per 100 person-months. The IR of SREs before any BTA use was 4.16 (95% CI, 3.71-4.65) per 100 person-months, and after any use was 3.60 (95% CI, 3.32-3.91) per 100 person-months. Conclusions: In this large cohort of elderly men with CRPC in a real-world setting in the U.S., SREs were common, with most occurring within a year after cohort entry. Although a direct causal interpretation of the difference in rates before and after BTA use is not possible (since confounding by indication and other factors cannot be excluded), further analysis may address at least some potential confounders.

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.

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