scholarly journals Outcome Differences Between First- and Second-generation EGFR Inhibitors in Advanced EGFR Mutated NSCLC in a Large Population-based Cohort

2019 ◽  
Vol 20 (5) ◽  
pp. e576-e583 ◽  
Author(s):  
Sally C. Lau ◽  
Negar Chooback ◽  
Cheryl Ho ◽  
Barbara Melosky
Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3393-3393 ◽  
Author(s):  
Suely M Rezende ◽  
Willem M. Lijfering ◽  
Frits R. Rosendaal ◽  
Suzanne C. Cannegieter

Abstract Abstract 3393 Background: Ethnic differences in the incidence of venous thrombosis have been appreciated for many years. However, with few exceptions, most of the studies on this subject were based on administrative databases from North America and China. The aim of this study was to investigate the risk of venous thrombosis in different first and second generation immigrant groups included in a large population-based case-control study, performed in the Netherlands. Methods: This study was performed using data from the MEGA study (Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis-study), a large, population based case-control study on risk factors for venous thrombosis from the Netherlands. Inclusion criteria consisted of patients and controls whom information were available on the country of birth. For the analysis related to immigration background, patients were compared with random digit dialing (RDD) controls. First generation immigrants were classified as those who were born outside the Netherlands. Second generation immigrants were similarly defined as first generation immigrants, except that second immigrants were born in the Netherlands, while both parents were born in one of aforementioned other countries. In total, 6899 participants were included, of whom 4300 patients and 2599 RDD controls. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated as estimates of the relative risk, and were adjusted for age, sex, body mass index, smoking, hormonal factors, alcohol consumption, physical activity and malignancy by unconditional logistic regression. Results: The risk of venous thrombosis varied according to the region of birth (Table 1). When compared with the Dutch, Eastern Europeans reached the highest and East/Southeast Asians the lowest risk of venous thrombosis with OR of 2.35, (95% CI, 1.09–4.59) and 0.44 (95% CI, 0.29–0.68), respectively after multivariate adjustments. Caribeans showed an intermediate lower risk of 0.69 (95% CI, 0.36–1.30) after multivariate adjustments (Table 1). We did not observe a major difference on the risk for VT between first and second generation immigrants, although the number of second generation immigrants was small for some groups. Subgroup analysis did not show major differences according to immigration groups, except for Eastern Europeans, who had a higher risk for unprovoked event with OR of 3.79 (95% CI, 1.44–9.97) and East/Southeast Asians with higher risk for pulmonary embolism with OR of 0.60 (95% CI, 0.36–1.0) (Table 2). In comparison with Dutch controls, East/Southeast Asians controls had lower prevalence of factor V Leiden (6% and 1%, respectively) and prothrombin mutation (2% and 1%, respectively) but higher blood group non-O (54% and 62%, respectively). Risk of VT in East/Southeast Asians adjusted for age, sex, factor V Leiden and blood group non-O was 0.53 (95% CI, 0.35–0.80). Analysis of a panel of procoagulant, anticoagulant, profibrinolytic and genetic factors are underway and is expected to be available before the ASH conference of 2012. Conclusions: The risk of VT varies in different populations. The risk of VT in East/Southeast Asians was the lowest and was virtually unchanged after adjustment for several environmental and genetic known risk factors for VT. Disclosures: No relevant conflicts of interest to declare.


Brain ◽  
2019 ◽  
Vol 142 (6) ◽  
pp. 1587-1597 ◽  
Author(s):  
Nete Munk Nielsen ◽  
Giulia Corn ◽  
Morten Frisch ◽  
Egon Stenager ◽  
Nils Koch-Henriksen ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Dan Shao ◽  
Dongyang Du ◽  
Haiping Liu ◽  
Jieqin Lv ◽  
You Cheng ◽  
...  

ObjectivesThis project aimed to construct an individualized PET/CT prognostic biomarker to accurately quantify the progression risk of patients with stage IIIC-IV epidermal growth factor receptor (EGFR)-mutated Non-small cell lung cancer (NSCLC) after first-line first and second generation EGFR- tyrosine kinase inhibitor (TKI) drug therapy and identify the first and second generation EGFR-TKI treatment-sensitive population.MethodsA total of 250 patients with stage IIIC-IV EGFR-mutated NSCLC underwent first-line first and second generation EGFR-TKI drug therapy were included from two institutions (140 patients in training cohort; 60 patients in internal validation cohort, and 50 patients in external validation cohort). 1037 3D radiomics features were extracted to quantify the phenotypic characteristics of the tumor region in PET and CT images, respectively. A four-step feature selection method was performed to enable derivation of stable and effective signature in the training cohort. According to the median value of radiomics signature score (Rad-score), patients were divided into low- and high-risk groups. The progression-free survival (PFS) behaviors of the two subgroups were compared by Kaplan–Meier survival analysis.ResultsOur results shown that higher Rad-scores were significantly associated with worse PFS in the training (p < 0.0001), internal validation (p = 0.0153), and external validation (p = 0.0006) cohorts. Rad-score can effectively identify patients with a high risk of rapid progression. The Kaplan–Meier survival curves of the three cohorts present significant differences in PFS between the stratified slow and rapid progression subgroups.ConclusionThe PET/CT-derived Rad-score can realize the precise quantitative stratification of progression risk after first-line first and second generation EGFR-TKI drug therapy for NSCLC and identify EGFR-mutated NSCLC populations sensitive to targeted therapy, which might help to provide precise treatment options for NSCLC.


2017 ◽  
Vol 41 (S1) ◽  
pp. s249-s249 ◽  
Author(s):  
P. Schofield ◽  
J. Das-Munshi ◽  
L. Becares ◽  
E. Agerbo

IntroductionLiving in an area with few people from the same ethnic background has been associated with increased incidence of psychosis (the ethnic density effect).ObjectivesCompare associations between neighbourhood ethnic density and incidence of non-affective psychosis for first and second generation migrants.MethodsPopulation based cohort (2.2 million) of all those born 1st January 1965 or later and living in Denmark on their 15th birthday. We looked at a total of 106,000 migrants, including 62% first generation migrants. Ethnic density was determined at age 15 and we adjusted for age, gender, calendar period, parental psychiatric history and parental income at age 15.ResultsFor the first generation, we found no evidence that rates of non-affective psychosis were related to neighbourhood ethnic density for migrants from Africa (comparing lowest and highest quintiles): IRR 1.02 (95% CI 0.6–1.73), and the Middle East: IRR 0.96 (CI 0.68–1.35) and only weak evidence for migrants from Europe (excluding Scandinavia): IRR 1.35 (CI 0.98–1.84). Conversely, for the second generation rates of non-affective psychosis were increased for migrants from Africa in lower ethnic density neighbourhoods (comparing lowest and highest quintiles): IRR 3.97 (95% CI 1.81–8.69), Europe (excluding Scandinavia): IRR 1.82 (CI 1.28–2.59) and the Middle East: IRR 2.42 (CI 1.18–4.99).ConclusionsThere is strong evidence for an area ethnic density effect on psychosis incidence for second generation migrants, but not for first generation migrants. This could reflect a greater resilience among the latter group to the adverse effects of minority status.Disclosure of interestThe authors have not supplied their declaration of competing interest.


2018 ◽  
Vol 104 (6) ◽  
pp. NP29-NP33 ◽  
Author(s):  
Francesco Facchinetti ◽  
Francesca Bozzetti ◽  
Roberta Minari ◽  
Giovanni Ceccon ◽  
Teresa Zielli ◽  
...  

Introduction: Treatment paradigms for EGFR-mutated non-small cell lung cancer (NSCLC) have successfully evolved since the introduction of osimertinib. The detection of EGFR T790M mutation in plasma or tumor samples obtained at disease progression to first-/second-generation EGFR inhibitors is mandatory for osimertinib prescription. Nevertheless, pharmacokinetics properties of osimertinib guarantee its usefulness in central nervous system (CNS) disease even in the case of T790M-negative or unknown status. Patients and methods: In this brief report, we share the clinical histories of two patients with CNS-preeminent progression under first-/second-generation EGFR inhibitors in which it was not possible to document the presence of T790M resistance mutation. Results: Patient outcomes diverged dramatically due to the differential availability of off-label osimertinib. Conclusions: Waiting for the novel molecule to be approved and licensed in first-line treatment, our report of hope and frustration is intended to stress the opportunity of its administration in the case of CNS failure of first-line EGFR inhibition, even in the absence of T790M proof.


2019 ◽  
Vol 14 (10) ◽  
pp. S553-S554
Author(s):  
M. Canale ◽  
E. Petracci ◽  
L. Crino ◽  
N. De Luigi ◽  
V. Ludovini ◽  
...  

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