Dataset Information

Consistent LDL-C response with evolocumab among patient subgroups in PROFICIO: A pooled analysis of 3146 patients from phase 3 studies.

ABSTRACT:

Background

Evolocumab significantly lowers low-density lipoprotein cholesterol (LDL-C) when dosed 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM) subcutaneously.

Hypothesis

LDL-C changes are comparable among different patient subgroups in a pooled analysis of data from phase 3 trials.

Methods

A total of 3146 patients received ≥1 dose of evolocumab or control in four 12-week phase 3 studies. Percent change from baseline in LDL-C for evolocumab 140 mg Q2W or 420 mg QM vs control was reported as the average of week 10 and 12 values. Quantitative and qualitative interactions between treatment group and subgroup by dose regimen were tested.

Results

In the pooled analysis, treatment differences vs placebo or ezetimibe were similar for both 140 mg Q2W and 420 mg QM doses across ages (<65 years, ≥65 years); gender; race (Asian, black, white, other); ethnicity (Hispanic, non-Hispanic); region (Europe, North America, Asia Pacific); glucose tolerance status (type 2 diabetes mellitus, metabolic syndrome, neither); National Cholesterol Education Program risk categories (high, moderately high, moderate, low); and European Society of Cardiology/European Atherosclerosis Society risk categories (very high, high, moderate, or low). Certain low-magnitude variations in LDL-C lowering among subgroups led to significant quantitative interaction P values that, when tested by qualitative interaction, were not significant. The incidences of adverse events were similar across groups treated with each evolocumab dosing regimen or control.

Conclusions

Consistent reductions in LDL-C were observed in the evolocumab group regardless of demographic and disease characteristics.

SUBMITTER: Stroes E

PROVIDER: S-EPMC6489970 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundAccording to the Chinese guidelines for lipid management (2023), evolocumab in combination with statins was recommended as secondary prevention of cardiovascular disease. However, because of the variation in the price of evolocumab and its different methods of confirming clinical efficacy, it was necessary to explore its economics and the impact of different methods of confirming efficacy on its economic studies.ObjectiveThe purpose of this paper was to assess the cost-effectiveness of evolocumab with statins versus statins alone for patients with acute myocardial infarction(AMI) in China and to investigate the impact of different clinical effectiveness modeling approaches on economic outcomes.MethodsA Markov cohort state-transition model was used to estimate the incremental cost-effectiveness ratio (ICER) based on Chinese observational data on cardiovascular event rates, efficacy from the Asian subgroup of the FOURIER trial, cost and utility from the Chinese Yearbook of Health Statistics, health insurance data, and published studies conducted in China. This study conducted subgroup analyses for different populations and dosing regimens; sensitivity analyses for parameters such as cost, utility, and cardiovascular event rates; and scenario analyses on hospital hierarchy, time horizon, starting age, and price for statins.ResultsICERs ranged from 27423 to 214777 Chinese yuan(CNY) per QALY gained, all below the willingness-to-pay threshold of CNY 257094. Only when the time horizon became small, the ICERs were greater than the willingness-to-pay. The probabilities that adding evolocumab to statins was cost-effective ranged from 76 to 98%. When the time horizon became small, i.e. evolocumab was discontinued before the age of 75 (after conversion), the corresponding ICERs were almost always greater than the willingness-to-pay. ICERs for modelling approaches based on clinical endpoints were 1.34 to 1.95 times higher than ICERs for modelling approaches based on reduced LDL-C levels.ConclusionsFrom the Chinese healthcare and private payer perspectives, adding evolocumab to statin therapy in AMI patients is more likely to be a cost-effective treatment option at the current list price of CNY 283.8. However, evolocumab may not be cost-effective if used for shorter periods of time. The results based on different clinical effectiveness modeling approaches were significantly different.

Project description:Trabectedin is reported as effective, especially against translocation-related sarcomas (TRSs) after failure of or intolerance to standard chemotherapy. We conducted two phase II studies of TRS, confirming high efficacy of 1.2 mg/m2 trabectedin. The updated data of 66 patients in these studies was integrated to evaluate the efficacy of trabectedin against each histological subtype, and analyze final overall survival (OS).Trabectedin was administered on day one of a 21-day cycle. Efficacy was assessed using progression-free survival (PFS), OS, and best overall response. An analysis of OS and PFS was performed for subgroups divided by baseline lymphocyte count (<1,000/μL, ≥1,000/μL) or number of previous chemotherapy regimens (0, 1, 2, ≥3 regimens), and a Weibull parametric model was used to estimate the numerical relationship between lymphocyte count and PFS and OS.Median PFS and OS in overall patients were 5.6 (95% confidence interval [CI]: 4.1-7.3) and 17.5 months (95% CI: 12.6-23.6), respectively. PFS in the myxoid and round-cell liposarcoma (MRCL) group (7.4 months [95% CI: 5.6-11.1]) was longer than in the other subtypes. The response rate was also highest in the MRCL group. Median OS was longer in patients with baseline lymphocyte counts ≥1,000/μL than in those with counts of <1,000/μL, but median PFS was not different between the two subgroups.Our updated and pooled data showed that trabectedin exerted prolonged disease control and antitumor effects in patients with advanced TRS, especially in MRCL. We consider that the subgroup analyses also provide important information for trabectedin treatment in patients with TRS.The progression-free survival (PFS) for the integrated data of 66 patients with translocation-related sarcomas (TRSs) in two phase II studies of trabectedin 1.2 mg/m2 was 5.6 months (95% confidence interval: 4.1-7.3). PFS and response rate in myxoid/round-cell liposarcoma was longer than that of other subtypes. The overall survival (OS) in all TRS subtypes was similar to previous data of TRS patients. In subgroup analysis, the patients with baseline lymphocyte count ≥1,000/μL exhibited better OS, although PFS was not different by baseline lymphocyte count. Our data are considered important information for trabectedin treatment in TRS patients.