EGFR mutational status in a large series of Caucasian European NSCLC patients: data from daily practice

Abstract

Background:The prognosis of metastatic non-small cell lung cancer (NSCLC) is still poor. Activating epithelial growth factor receptor (EGFR) mutations are important genetic alterations with dramatic therapeutical implications. Up to now, in contrast to Asian populations only limited data on the prevalence of those mutations are available from patients with Caucasian and especially European ethnicity.Methods:In this multicentre study, 1201 unselected NSCLC patients from Southern Germany were tested in the daily clinical routine for EGFR mutation status.Results:Activating EGFR mutations were found in 9.8% of all tumours. Mutations in exons 18, 19 and 21 accounted for 4.2%, 61.9% and 33.1% of all mutations, respectively. Non-smokers had a significantly higher rate of EGFR mutations than smokers or ex-smokers (24.4% vs 4.2% P<0.001). Non-lepidic-non-mucinous adenocarcinomas (G2) accounted for 45.5% of all activating EGFR mutations and 3.5% of all squamous cell carcinomas were tested positive. Thyroid transcription factor 1 protein expression was significantly associated with EGFR mutational status.Conclusion:These comprehensive data from clinical routine in Germany add to the knowledge of clinical and histopathological factors associated with EGFR mutational status in NSCLC.

Efficacy of tyrosine kinase inhibitors in non-small-cell lung cancer patients undergoing dose reduction and those with a low body surface area

“…In addition, 46.4% of the 282 patients had a BSA of <1.5 m 2 , demonstrating that a considerable percentage of patients with low BSA received TKI therapy, which may be associated with the fact that a number of those patients were EGFR-mutated female patients. In fact, in previous reports on treatment with TKIs, either in clinical trials or clinical practice, there was a higher population of female patients with NSCLC compared to that in the general population (7)(8)(9)16).…”

“…However, body size was not taken into consideration in previous dose-finding studies. A significant number of EGFR-mutated patients are female and, in their majority, the body surface area (BSA) may be low (7)(8)(9). Therefore, a dose reduction due to AEs or low BSA may be required in daily clinical practice for such patients.…”

Predictors of EGFR mutation and factors associated with clinical tumor stage at diagnosis: Experience of the INSIGHT study in Poland

“…These results have led to a consensus that the presence of EGFR mutations is a strong predictor of TKI treatment response and various associations and working groups, internationally and in Poland, now recommend screening newly diagnosed patients with advanced NSCLC for specific mutations in order to customize the modality of treatment (9,(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). Despite these, the incidence rates of EGFR mutations are found to vary substantially between different regions and countries (8,10,15). Possible reasons for this discrepancy could be lack of clarity in selection criteria for EGFR-positivity testing, differences in molecular methods employed for screening, and issues with sampling and tissue preservation.…”

“…These cause a loss in autoinhibition of the tyrosine kinase and a continually activated state of its kinase function. Deletion in exon 19 and a L858R (leucine to arginine substitution at position 858) substitution in exon 21 comprise approximately 90% of EGFR mutations found in adenocarcinomas of the lung (7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Patients with diagnosed mutations in EGFR are referred to as EGFR-positive.…”

Emerging resistance pathways in lung cancer: what has ROS-1 taught us?

“…Selection of molecularly targeted systemic therapy is commonly based on clonal oncogenic drivers of which epidermal growth factor receptor (EGFR) and the fusion gene echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EMLA4-ALK) are examples established in clinical practice. The former, found in approximately 10-15% of patients with NSCLC in the western world, is more prevalent in adenocarcinoma, non/light smokers, younger females, and patients of far eastern descent (1). Patients with EMLA4-ALK translocated tumors share similar clinical characteristics but are less prevalent (2).…”