ObjectivesThe objective of this study was to determine the nature of evidence used to support the withdrawal of marketing authorisations of drug products for safety reasons throughout the European Union (EU) between 2002 and 2011.SettingProducts withdrawn, either by a medicines agency or a marketing authorisation holder, during the period 2002–2011 were identified by conducting detailed searches of the WHO, the European Medicines Agency (EMA) and national medicines agency websites throughout the EU plus Norway, Iceland and Liechtenstein. The scientific evidence used to support the decision was identified from a search within PubMed, the EMA and national medicines agencies websites. Information about spontaneous case reports entered into EudraVigilance and unavailable on the EMA website was received by email from the EMA.Results19 drugs were withdrawn from the market, throughout the EU, for safety reasons from 2002 to 2011. Case reports were cited in 95% of withdrawals (18/19) and case–control studies (4/19), cohort studies (4/19), randomised controlled trials (RCTs) (12/19) or meta-analysis (5/19) were cited in 63% of withdrawals (12/19). Cardiovascular events or disorders were the main reason for withdrawal (9/19), followed by hepatic disorders (4/19) and neurological or psychiatric disorders (4/19).ConclusionsThis study has shown that the level of evidence used to support drug withdrawal has improved during the past 10 years, with an increased use of case–control studies, cohort studies, RCTs and meta-analyses. This research has demonstrated that such studies have contributed to decision-making in almost two-thirds of cases.
premenopausal and postmenopausal, 66. 7% and 33.3% had MRM and BCS, respectively. Stage II and III represented 73.3% and 33.3%, respectively. In the post chemotherapy evaluation there was a statistically significant difference between hypothermic and control arms as regards ulnar and superficial radial SNAP amplitude, ulnar CMAP amplitude and ulnar motor DL (p value 0.005, 0.043, 0.001, and 0.008, respectively) but no difference regarding SCV in ulnar and radial nerves. In contrast, the pre chemotherapy evaluation showed no statistically significant difference between both arms in any of the studied parameters.Conclusions: Limb hypothermia had a potential protective effect against paclitaxel induced peripheral neuropathy in both sensory and motor fibers, indicating that it could be a promising solution in decreasing CIPN.
IntroductionFluenz Tetra is an intranasal quadrivalent live attenuated influenza vaccine (QLAIV) and is recommended as the vaccine of choice for children in the 2014/2015 influenza season vaccination programme in the UK.ObjectiveThe primary objective of the study was to estimate the crude incidence rate of adverse events of interest (AEIs) following vaccination with the nasal QLAIV early in the 2014/2015 influenza season in children and adolescents in England.MethodsA pilot non-interventional cohort post-authorisation safety study (PASS) was conducted during the 2014/2015 influenza season in England. Vaccinees were recruited via the mass vaccination programme in England. Participant outcomes, validated by a healthcare professional (general practitioner) where appropriate, were captured through questionnaires (surface mail, telephone, e-questionnaire). Data analysis comprised descriptive statistics and calculation of event risks and incidence rates, stratified by age group and selected co-morbidities.ResultsThe final evaluable cohort consisted of 385 participants; the median (interquartile range) age was 4 (3–9) years with a range of 2–17 years, and 53.2 % were female. The most frequently reported AEI was nasal congestion (n = 167; 43.4 %; 312.3 per 1000 patient-weeks [95 % CI 267.3–364.8]). Further frequently reported AEIs were malaise (n = 87; 22.6 %; 123.4 per 1000 patient-weeks [95 % CI 98.9–154.1]) and cough (n = 80; 20.8 %; 118.5 per 1000 patient-weeks [95 % CI 95.1–147.8]). Five hypersensitivity-type reactions were reported, although on follow-up none were true hypersensitivity reactions or required hospitalisation. No serious adverse events (SAEs) were reported, with no hospitalisations or deaths. No significant change in reactogenicity or other apparent safety signals was detected as part of this study.ConclusionThe pilot study showed no significant change in reactogenicity or other apparent safety signals from the data collected. Continued enhanced surveillance of seasonal influenza vaccines will ensure their ongoing safety for the prevention of serious illness from seasonal influenza outbreaks.Electronic supplementary materialThe online version of this article (doi:10.1007/s40264-015-0384-7) contains supplementary material, which is available to authorized users.
Background: Abemaciclib is an orally administered, selective small molecule cyclin-dependent kinase (CDK) 4 and 6 inhibitor, approved to treat HR+, HER2- mBC pts on a continuous twice daily dosing schedule as monotherapy or in combination with endocrine therapy (ET), an aromatase inhibitor as initial endocrine based therapy, or in combination with fulvestrant. In preclinical models, abemaciclib monotherapy induced intra-tumoral immune inflammation and had a synergistically enhanced anti-tumor efficacy when administered in combination with programmed cell death protein 1 blockade. Here we report the safety and preliminary anti-tumor activity of abemaciclib plus pembrolizumab plus anastrozole in HR+, HER2- locally advanced or mBC pts. Methods: This multicenter, nonrandomized, open-label, multi-cohort phase 1b study of abemaciclib plus pembrolizumab plus anastrozole enrolled a cohort of post-menopausal HR+, HER2- pts with locally advanced or mBC. No prior CDK4/6 inhibitor, chemotherapy, or ET for locoregional advanced or mBC were allowed. Patients received 150-mg abemaciclib orally every 12 hours plus pembrolizumab 200 mg intravenously on day 1 every 21 days plus anastrozole 1 mg orally every 24 hours. The primary objective was to characterize the safety of abemaciclib plus pembrolizumab plus anastrozole. Key secondary objectives included objective response rate (ORR), progression-free survival, and overall survival. Results: Out of 26 pts enrolled, 13 (50%) had received prior systemic anti-cancer therapy, including 12 (46%) who had received ET in the adjuvant setting. The majority of pts had visceral disease (65%); 54% had 3 or more metastatic sites. The nature of adverse events (AEs) observed for the triplet therapy was overall consistent with the known side effects of abemaciclib, pembrolizumab and anastrozole. Grade 3/4 AEs in > 2 pts included increased alanine aminotransferase and neutropenia (8 pts each, 31%) and increased aspartate aminotransferase (6 pts, 23%). In general, Grade 3/4 AEs were reversible following drug holds and corticosteroid treatment. There were 2 fatal events as a result of pneumonitis. Fifteen pts (58%) discontinued treatment including 9 pts (35%) due to an AE (7 transaminase elevations). Preliminary response assessment showed 5 pts had a confirmed partial response (19% ORR), and disease control rate (CR+PR+SD) was 77%. Clinical benefit rate (CR+PR+SD persisting for ≥6 months) was 27%. Conclusions: Abemaciclib plus pembrolizumab plus anastrozole demonstrated a numerically higher rate of transaminase elevations and pneumonitis than reported for the individual treatments and 2 experienced a fatal AE. At this time, evaluation of anti-cancer activity is premature. Citation Format: Hope S. Rugo, J. Thad Beck, Guy Jerusalem, Hans Wildiers, Peter Kabos, Michael Chisamore, Rhian McNaughton, Yanyun Chen, Anwar Hossain, Sara M. Tolaney. A phase 1b study of abemaciclib in combination with pembrolizumab for patients (pts) with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (mBC) (NCT02779751): Preliminary results [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT108.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.