Impact of Continuing First-Line EGFR Tyrosine Kinase Inhibitor Therapy Beyond RECIST Disease Progression in Patients with Advanced EGFR-Mutated Non-Small-Cell Lung Cancer (NSCLC): Retrospective GFPC 04-13 Study
Auliac J.B.,Service de pneumologie et oncologie thoracique |
Bizieux A.,Roche Holding AG |
Decroisette Phan van Ho C.,Prigny
Targeted Oncology | Year: 2015
Retrospective studies suggested a benefit of first-line tyrosine kinase inhibitor (TKI) treatment continuation after response evaluation in solid tumors (RECIST) progression in epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients. The aim of this multicenter observational retrospective study was to assess the frequency of this practice and its impact on overall survival (OS). The analysis included advanced EGFR-mutated NSCLC patients treated with first-line TKI who experienced RECIST progression between June 2010 and July 2012. Among the 123 patients included (67 ± 12.7 years, women: 69 %, non smokers: 68 %, PS 0–1: 87 %), 40.6 % continued TKI therapy after RECIST progression. There was no difference between the patients who did and did not continue TKI therapy with respect to progression-free survival (PFS1: 10.5 versus 9.5 months, p = 0.4). Overall survival (OS) showed a non-significant trend in favor of continuing TKI therapy (33.0 vs. 21.2 months, p = 0.054). Progressions were significantly less symptomatic in the TKI continuation group than in the discontinuation group (18 % vs. 37 %, p < 0.01). Univariate analysis showed a higher risk of death among patients with PS >1 (HR 4.33, 95 %CI: 2.21-8.47, p = 0.001), >1 one metastatic site (HR 1.96, 95 %CI: 1.06-3.61, p = 0.02), brain metastasis (HR 1.75, 95 %CI: 1.08-2.84, p = 0.02) at diagnosis, and a trend towards a higher risk of death in cases of TKI discontinuation after progression (HR 1.62, 95 %CI: 0.98-2.67, p = 0.056 ). In multivariate analysis only PS >1 (HR 6.27, 95 %CI: 2.97-13.25, p = 0.00001) and >1 metastatic site (HR 2.54, 95 %CI: 1.24-5.21, p = 0.02) at diagnosis remained significant. This study suggests that under certain circumstances, first-line TKI treatment continuation after RECIST progression is an acceptable option in EGFR-mutated NSCLC patients. Clinical trial information: NCT02293733 © 2015 Springer International Publishing Switzerland
Couraud S.,Service de pneumologie et oncologie thoracique |
Couraud S.,University Claude Bernard Lyon 1 |
Wislez M.,Service de pneumologie |
Wislez M.,University Pierre and Marie Curie
Revue des Maladies Respiratoires Actualites | Year: 2014
A never-smoker is a defined as a subject who smoked less than 100 cigarettes in his/her lifetime. About one quarter of all lung cancers occurring worldwide is thought to happen in such patients and 300,000 deaths are related to lung cancer in never-smoker (LCINS) each year.For most of authors, LCINS is a distinct entity. Actually, they occur mainly in women, are mostly adenocarcinoma, and arise particularly in Asia. Moreover, tumors have a specific. mutation profile among never-smoker: HER family (EGFR and HER2) mutations are common as well as ALK and ROS1 fusion gene.LCINS are also a perfect model for the study of non-tobacco related risk factors of lung cancer. These factors could be clustered in five families: inhaled toxic, professional pollutants, domestic pollutants, atmospheric pollutants and personal and familial medical history.Although LCINS is not rare and of high-interest, there are very few data on this entity, in particular in Europe. Indeed, epidemiology of LCINS is strongly affected by geographical origin of patients and features observed in Europe should be different from those observed in Asia or North America. © 2013 Elsevier Masson SAS.
Couraud S.,Service de Pneumologie et dOncologie Thoracique |
Couraud S.,University of Lyon |
Fournel P.,Institute Of Cancerologie Of La Loire |
Moro-Sibilot D.,Grenoble University Hospital Center |
And 3 more authors.
Clinical Lung Cancer | Year: 2011
Background: In 2003 the French government initiated a large cancer plan. This program requested the latest edition of local guidelines in each of France's administrative regions. Since their creation, none of these guidelines has been assessed in the conditions of daily clinical practice. Method: A survey was performed to assess physicians' integrated knowledge of local guidelines in the Rhne-Alpes region in France. It included 4 patient cases with accompanying multiple-choice questions. Responses were judged as appropriate or inappropriate according to the 2007 edition of local guidelines. Results: Four hundred one physicians were contacted. The response rate was 56%. Among the responding physicians, 71 were eligible for analysis (those who were board certified in oncology and pulmonology and practiced thoracic oncology only). The rate of physicians who applied guidelines was 55%, 54%, 63%, and 25% for cases 1 to 4, respectively. There were no major differences in the responses between oncologists and pulmonologists. However significant differences were noted between physicians working in public health centers (cases 1 and 2) and those who practiced in private centers (cases 3 and 4) (appropriate response rate, 68% [case 3] vs. 36% [case 1] [P =.0494] for case 1; 28% [case 4] vs. 9% [case 2] (P =.0022)). Finally, no differences in physician responses were found in the administrative departments within the administrative region. Conclusion: The results of the survey illustrate that regional guidelines are not routinely applied in daily clinical practice. This nonapplication of regional guidelines by physicians may be due to either a lack of knowledge of updates to guidelines or a lack of agreement with them. © 2011 Elsevier Inc. All rights reserved.
Balduyck M.,Lille 2 University of Health and Law |
Odou M.-F.,Lille 2 University of Health and Law |
Porchet N.,French Institute of Health and Medical Research |
Lafitte J.-J.,Service de pneumologie et oncologie thoracique |
Maitre B.,University Paris Est Creteil
Revue des Maladies Respiratoires | Year: 2014
Alpha-1-antitrypsin (A1AT) deficiency is an autosomal recessive genetic disorder, which predisposes affected patients to development of pulmonary emphysema or liver cirrhosis. Despite the guidelines from the American Thoracic Society and the European Respiratory Society about A1AT deficiency screening, it remains significantly under recognized. So, it seems necessary to propose an efficient and suitable biological approach to improve diagnosis and management of A1AT deficiency. A1AT is a 52 kDa glycoprotein predominantly produced in the liver and its physiological serum concentration for adults' ranges from 0.9 to 2.0 g/L (17 to 39 μmol/L). It is encoded by the SERPINA1 gene, which is highly pleomorphic and to date, more than 100 alleles have been identified. A1AT testing would initially involve quantification of serum A1AT concentration with possible complementary measurement of the elastase inhibitory capacity of serum. If the serum A1AT concentration is reduced below the reference value, two strategies for laboratory testing can be used: (i) serum A1AT phenotyping by isoelectric focusing which allows identification of the most common variant designated as the PI M variant but also of various deficient variants besides the predominant PI S and PI Z ones, (ii) genotyping by allele-specific PCR methods which allows only identification of the deficient PI S and PI Z allele. Identification of the Null alleles or of other rare deficient alleles can be performed by direct sequencing of the whole SERPINA1 gene as a reflex test. © 2014 SPLF.
Boespflug A.,Service de pneumologie et oncologie thoracique |
Boespflug A.,Charles University |
Couraud S.,Service de pneumologie et oncologie thoracique |
Couraud S.,Charles University |
And 8 more authors.
Lung Cancer | Year: 2013
Cowden's syndrome is a rare autosomal dominant disorder that has been linked to germline mutations in the phosphatase and TENsin homolog (PTEN) gene. PTEN is a tumour suppressor gene that negatively regulates the PI3K-AKT-mTOR pathway. Cowden's syndrome is a multi-system disease with increased risks for a number of malignancies but very rarely for lung cancer.A systematic follow-up chest CT scan was performed to a 42 year's old female, light smoker. It showed a 20. mm opacity of the left upper pulmonary lobe. Differential diagnose with benign tumours (such as hamartoma) was carefully searched. Procedures led to the diagnosis of a primitive lung adenocarcinoma. EGFR sequencing shows two rare somatic mutations (S768I and V769L).Lack of expression of PTEN is a non-sufficient condition leads to lung cancer formation alone. Nevertheless, it increases cell oncogenic potential. PTEN lacking in non small cell lung cancer is a frequent issue. It could be an alternative mechanism of non-efficacy of EGFR-TKI in cells with a sensitizing EGFR mutation.This case report, a very rare entity: a patient with a PTEN germline mutation and a lung adenocarcinoma harbouring two concomitant rare somatic mutations of EGFR. This observation comforts PTENs role in lung oncogenesis. © 2012 Elsevier Ireland Ltd.