Background and importanceMany studies support pembrolizumab (a humanised monoclonal antibody directed towards programmed cell death protein-1 (PD-1)) as the firstline treatment of advanced non-small ...cell lung cancer (NSCLC) without EGFR/ALK alterations.Aim and objectivesThe aim of this observational was to report clinical outcome in terms of overall survival (OS) analysis, as well as in stratified OS, in subgroups of patients.Material and methodsBetween 1 July 2017 and 28 February 2020, 98 patients with NSCLC were eligible to be treated with pembrolizumab (200 mg q3w fixed dose). The last follow-up date was 24 August 2020. Clinical data, such as expression of PD-L1, performance status (ECOG-PS), treatment duration, toxicity (CTCAE V.5.0) and outcome were collected from the local electronic medical records. OS, defined as the time from the start of therapy to death or last follow-up, was compared in subgroups of patients using the log rank test (with R software); p<0.05 was considered statistically significant.ResultsThis investigation provided preliminary results for 98 patients (of whom 64% were male). Median age was 73 years (range 44–89). ECOG-PS was 0 or 1 in 91% of cases and 29.6% of patients had a PD-L1 >90%. Median duration of treatment was seven cycles. At a median follow-up of 14.6 months, the percentage of patients still alive was 51% and median OS was 13.3 months (95% CI 10.5 to 31.4). The analysis revealed that OS was not influenced by sex or PD-L1, but significantly associated with ECOG-PS (p<0.001). Immunorelated adverse events occurred in 75.5% of patients (29.6% cutaneous, 24.5% gastrointestinal and 19.4% endocrinological). Patients with toxicity showed a significantly higher median OS (29.6 months, 95% CI 12.2 to NA) compared with those without significant toxicity (6.5 months, 95% CI 1.3 to 13.1, p=0.002).Conclusion and relevanceThese real life findings in the setting of advanced NSCLC patients with PD-L1 TPS ≥50% demonstrated the effectiveness of pembrolizumab. A median OS of 13.3 months was similar to that estimated in the real world Pembreizh study (15.3 months). The detection rate of AE of 75.5% was comparable with 73.4% in the KEYNOTE-024 study. However, pembrolizumab as mono-immunotherapy represents the standard of care as firstline treatment but results from trials evaluating combinations with chemotherapy (KEYNOTE189) could further change the therapeutic approaches.References and/or acknowledgementsConflict of interestNo conflict of interest
Decoherence and 1/ f noise in Josephson qubits Paladino, E; Faoro, L; D'Arrigo, A ...
Physica. E, Low-dimensional systems & nanostructures,
05/2003, Letnik:
18, Številka:
1
Journal Article
Recenzirano
Odprti dostop
We analyse decoherence in Josephson qubits induced by background charges responsible for 1/
f noise. To this end we introduce a quantum mechanical model of a discrete environment. The discrete nature ...of the environment leads to a number of new features which are mostly pronounced for slowly moving charges.
It is well known that it is possible to build quantum gates based entirely on the action of geometric phases. This approach is called holonomic quantum computation. Here we show that it is possible ...to generate and detect non‐Abelian geometric phases in the charge dynamics of a network of mesoscopic Josephson junctions. The scheme can be used to realize a universal set of quantum gates.
The April Case of the Month (COM). The contributors report a case of a 70 year-old woman with recurrent meningiomas, one of which showed rhabdoid and lipomatous differentiation. Histopathological ...study of the first and second previous resections showed only typical meningothelial meningioma. On the third craniotomy, a new tumor specimen showed an admixture of classic meningothelial meningioma with lipomatous and rhabdoid foci. Immunohistochemical studies showed diffuse reactivity for epithelial membrane antigen and vimentin, as well as focal positivity for desmin and smooth muscle actin in the areas with rhabdoid features and S100 protein in the lipomatous foci. The presence of these three different and concomitant histological patterns only in the third surgical resection might support a metaplastic origin and, also, corroborates the concept that rhabdoid features are suggestive of an aggressive behavior.
Abstract
Background: Personalized healthcare tailors treatments to patients and their disease characteristics through the use of genetics and other biomarkers. Genetic differences among individuals ...may explain variations in drug treatment response, including side effects. With such information physicians could make more informed decisions about drugs and dosing for a given individual, thereby improving patient care. Although there has been some success, to a large extent genetic variation related to drug response remains unexplained.
Bevacizumab, a humanized monoclonal antibody against the angiogenic factor VEGF, has demonstrated activity in patients with metastatic breast cancer (MBC). The InVite study will evaluate the feasibility of performing genomewide association studies using self-reported information collected via an online platform from patients with MBC who have been treated with bevacizumab. Using novel methodology in a convenient, user-friendly, and scientifically rigorous format, InVite ultimately aims to identify potential pharmacogenetic associations in this patient population.
Trial design: InVite is a pilot, non-interventional, observational, web-based, prospective cohort study designed to collect patient-reported safety, efficacy, and genetic data from patients with MBC treated with bevacizumab. Data on demographics, breast cancer disease status, cancer treatment history, bevacizumab-related outcomes, and certain safety events will be collected directly from patients entirely via online surveys. Patients will be asked to complete surveys at the time of enrollment and then every 3 months for 1 year after enrollment. A saliva sample for DNA collection will be gathered using an at-home kit. Evaluations of data quality and collection feasibility will be conducted intermittently. There will be an optional substudy to allow for blood sample collection for DNA analysis.
Eligibility criteria: ≥18 years of age, residing in the US, locally recurrent breast cancer or MBC, currently being or having been treated with bevacizumab starting on or before Dec 31, 2011, fluent in English, and access to a computer with an internet connection.
Specific aims: The primary objective is to assess the feasibility of recruiting subjects and collecting biospecimens and self-reported data online. The secondary objective is to characterize the patient population. Exploratory objectives include analyzing potential associations between genetic polymorphisms and 1) bevacizumab-induced hypertension, the most common bevacizumab-related adverse event, and 2) patient-reported time-to-progression.
Statistical methods: Baseline demographics, clinical and treatment characteristics of enrolled patients will be summarized. Each polymorphism genotyped will be tested for association with the defined endpoint using appropriate statistical modeling.
Present and target accrual: Accrual as of May 23, 2012 is 82 patients. Target accrual is 1000 patients.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT3-4-04.
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