Dataset Information

Real-World Evidence Prediction of a Phase IV Oncology Trial: Comparative Degarelix vs Leuprolide Safety.

ABSTRACT:

Background

Medical and regulatory communities are increasingly interested in the utility of real-world evidence (RWE) for answering questions pertaining to drug safety and effectiveness but concerns about validity remain. A principled approach to conducting RWE studies may alleviate concerns and increase confidence in findings. This study sought to predict the findings from the PRONOUNCE trial using a principled approach to generating RWE.

Methods

This propensity-score (PS) matched observational cohort study utilized 3 claims databases to compare the occurrence of major adverse cardiovascular events (MACE) among initiators of degarelix vs. leuprolide. Patients were included if they had history of prostate cancer and atherosclerotic cardiovascular disease. Subjects were excluded if they didn't have continuous database enrollment in the year prior to treatment initiation, were exposed to androgen deprivation therapy or experienced an acute cardiovascular event within 30 days prior to treatment initiation, or had a history or risk factors of QT prolongation.

Results

There were 12,448 leuprolide and 1,969 degarelix study-eligible patients before matching, with 1,887 in each arm after PS-matching. The results for MACE comparing degarelix to leuprolide in the observational analysis (hazard ratio= 1.35; 95% confidence interval = 0.94-1.93) was consistent with the subsequently released PRONOUNCE result (hazard ratio = 1.28; 95% confidence interval = 0.59-2.79).

Conclusions

This study successfully predicted the result of a comparative cardiovascular safety trial in the oncology setting. Although the findings are encouraging, limitations of measuring cancer stage and tumor progression are representative of challenges in attempting to generalize whether claims-based RWE can be used as actionable evidence.

SUBMITTER: Merola D

PROVIDER: S-EPMC9403105 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Real-World Evidence Prediction of a Phase IV Oncology Trial: Comparative Degarelix vs Leuprolide Safety.

Merola David D Schneeweiss Sebastian S Sreedhara Sushama K SK Zabotka Luke E LE Quinto Kenneth K Concato John J Wang Shirley V SV

JNCI cancer spectrum 20220810

<h4>Background</h4>Medical and regulatory communities are increasingly interested in the utility of real-world evidence (RWE) for answering questions pertaining to drug safety and effectiveness but concerns about validity remain. A principled approach to conducting RWE studies may alleviate concerns and increase confidence in findings. This study sought to predict the findings from the PRONOUNCE trial using a principled approach to generating RWE.<h4>Methods</h4>This propensity-score (PS) matche ...[more]

PMID: 35947646

Similar Datasets

Project description:ImportanceWith a growing interest in the use of real-world evidence for regulatory decision-making, it is important to understand whether real-world data can be used to emulate the results of randomized clinical trials.ObjectiveTo use electronic health record and administrative claims data to emulate the ongoing PRONOUNCE trial (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease).Design, setting, and participantsThis retrospective, propensity-matched cohort study included adult men with a diagnosis of prostate cancer and cardiovascular disease who initiated either degarelix or leuprolide between December 24, 2008, and June 30, 2019. Participants were commercially insured individuals and Medicare Advantage beneficiaries included in a large US administrative claims database.ExposuresDegarelix or leuprolide.Main outcomes and measuresThe primary end point was time to first occurrence of a major adverse cardiovascular event (MACE), defined as death due to any cause, myocardial infarction, or stroke, analogous to the PRONOUNCE trial. Secondary end points were time to death due to any cause, myocardial infarction, stroke, and angina. Cox proportional hazards regression was used to evaluate primary and secondary end points.ResultsA total of 32 172 men initiated degarelix or leuprolide for prostate cancer; of them, 9490 (29.5%) had cardiovascular disease, and 7800 (24.2%) met the PRONOUNCE trial eligibility criteria and were included in this study. Overall, 165 participants (2.1%) were Asian, 1390 (17.8%) were Black, 663 (8.5%) were Hispanic, and 5258 (67.4%) were White. The mean (SD) age was 74.4 (7.4) years. Among 2226 propensity score-matched patients, no significant difference was observed in the risk of MACE for patients taking degarelix vs those taking leuprolide (10.18 vs 8.60 events per 100 person-years; hazard ratio [HR], 1.18; 95% CI, 0.86-1.61). Degarelix was associated with a higher risk of death from any cause (HR, 1.48; 95% CI, 1.01-2.18) but not of myocardial infarction (HR, 1.16; 95% CI, 0.60-2.25), stroke (HR, 0.92; 95% CI, 0.45-1.85), or angina (HR, 1.36; 95% CI, 0.43-4.27).Conclusions and relevanceIn this emulation of a clinical trial of men with cardiovascular disease undergoing treatment for prostate cancer, degarelix was not associated with a lower risk of cardiovascular events than leuprolide. Comparison of these data with PRONOUNCE trial results, when published, will help enhance our understanding of the appropriate role of using real-world data to emulate clinical trials.

Project description:ObjectivesThis study will compare the incidence of major adverse cardiovascular events (MACEs) with androgen deprivation therapy (ADT) among men with advanced prostate cancer who are being treated with a gonadotropin-releasing hormone (GnRH) antagonist versus a GnRH agonist.BackgroundTreatment of advanced prostate cancer with ADT might increase the risk of subsequent cardiovascular events among men with known atherosclerotic cardiovascular disease (ASCVD), but a recent meta-analysis suggested that this risk might be lower with ADT using a GnRH antagonist versus a GnRH agonist.MethodsPRONOUNCE is a multicenter, prospective, randomized, open, blinded endpoint trial that will enroll approximately 900 patients with advanced prostate cancer and pre-existing ASCVD who will be treated with ADT. Participants will be randomized to receive the GnRH antagonist degarelix or the GnRH agonist leuprolide as ADT for 12 months. The primary endpoint is time from randomization to first confirmed, adjudicated occurrence of a MACE, which is defined as a composite of all-cause death, nonfatal myocardial infarction, or nonfatal stroke through 12 months of ADT treatment. Baseline cardiovascular biomarkers (high-sensitivity C-reactive protein, high-sensitivity troponin T, and N-terminal pro-brain natriuretic peptide), as well as serial inflammatory and immune biomarkers, will be evaluated in exploratory analyses.ResultsAs of October 1, 2019, a total of 364 patients have been enrolled. The mean age is 74 years, 90% are white, 80% have hypertension or dyslipidemia, 30% diabetes mellitus, 40% have had a previous myocardial infarction, and 65% have had previous revascularization. Regarding prostate cancer features at randomization, 48% of the patients had localized disease, 23% had locally advanced disease, and 18% had metastatic disease.ConclusionsPRONOUNCE is the first prospective cardiovascular outcomes trial in advanced prostate cancer that will delineate whether the risk of subsequent cardiovascular events associated with ADT is lower with a GnRH antagonist versus a GnRH agonist for men with pre-existing ASCVD. (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease [PRONOUNCE]; NCT02663908).

Project description:BackgroundThe relative cardiovascular safety of gonadotropin-releasing hormone (GnRH) antagonists compared with GnRH agonists in men with prostate cancer and known atherosclerotic cardiovascular disease remains controversial.MethodsIn this international, multicenter, prospective, randomized, open-label trial, men with prostate cancer and concomitant atherosclerotic cardiovascular disease were randomly assigned 1:1 to receive the GnRH antagonist degarelix or the GnRH agonist leuprolide for 12 months. The primary outcome was the time to first adjudicated major adverse cardiovascular event (composite of death, myocardial infarction, or stroke) through 12 months.ResultsBecause of slower-than-projected enrollment and fewer-than-projected primary outcome events, enrollment was stopped before the 900 planned participants were accrued. From May 3, 2016, to April 16, 2020, a total of 545 patients from 113 sites across 12 countries were randomly selected. Baseline characteristics were balanced between study groups. The median age was 73 years, 49.8% had localized prostate cancer; 26.3% had locally advanced disease, and 20.4% had metastatic disease. A major adverse cardiovascular event occurred in 15 (5.5%) patients assigned to degarelix and 11 (4.1%) patients assigned to leuprolide (hazard ratio, 1.28 [95% CI, 0.59-2.79]; P=0.53).ConclusionsPRONOUNCE (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease) is the first, international, randomized clinical trial to prospectively compare the cardiovascular safety of a GnRH antagonist and a GnRH agonist in patients with prostate cancer. The study was terminated prematurely because of the smaller than planned number of participants and events, and no difference in major adverse cardiovascular events at 1 year between patients assigned to degarelix or leuprolide was observed. The relative cardiovascular safety of GnRH antagonists and agonists remains unresolved. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02663908.

Project description:ObjectiveTo compare surgical success, postoperative intraocular pressure and complication rates between trabeculectomy and XEN gelstent surgery in a cohort of glaucoma patients in a typical clinical setting.MethodsA retrospective cohort study of consecutive patients with refractory open-angle glaucoma including patients who underwent either stand-alone XEN gelstent insertion with Mitomycin C or trabeculectomy with Mitomycin C between 2016 and 2018 at the University Eye Hospital Mainz, Germany. Primary outcome measure was the proportion of surgical success 1 year after surgery. Patients with an IOP ≤18mmHg, an intraocular pressure reduction of >20% and in no need of revision surgery or topical medication were considered a complete surgical success. If topical therapy was necessary, they were considered a qualified success. Multivariable logistic regression analysis was carried out for the primary outcome including gender, age, preoperative intraocular pressure and number of medication classes used preoperatively as adjustment variables.Results171 eyes of 144 patients were included, including 82 eyes of 58 patients in the XEN group and 89 eyes of 86 patients in the trabeculectomy group. The primary outcome defined as the proportion of surgical success after 1 year (mean 11.1 months ± 2.2) was similar for both groups. The complete success proportion was 65.5% (95%-CI: 55.6-75.9%) in the trabeculectomy group, and 58.5% (95%-CI: 47.6-69.4%) in the XEN group and not statistically different in our analysis model (crude OR = 0.61; 95%-CI: 0.31-1.22; adjusted OR = 0.66; 95%-CI: 0.32-1.37). The intraocular pressure reduction, as secondary outcome measure, was higher in the trabeculectomy group (10.5 mmHg) compared to the XEN group (7.2 mmHg; p = 0.003) at the 12-month follow-up.ConclusionBoth XEN gelstent implantation and trabeculectomy show similar proportions of surgical success and of complications and are therefore both recommendable for clinical routine. However, trabeculectomy seems to be more effective in lowering intraocular pressure than the XEN implantation. A prospective randomized clinical trial is necessary to evaluate differences in the long-term clinical outcome.

Dataset Information

Real-World Evidence Prediction of a Phase IV Oncology Trial: Comparative Degarelix vs Leuprolide Safety.

Background

Methods

Results

Conclusions

Publications

Real-World Evidence Prediction of a Phase IV Oncology Trial: Comparative Degarelix vs Leuprolide Safety.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets