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

Abstract

Abstract. Targeted therapy of non-small cell lung cancer (NSCLC) patients with mutations in the epidermal growth factor receptor (EGFR) gene has been associated with improved prognosis. However, there is a shortage on data from real-world clinical practice in management of EGFR-positive NSCLC patients in Poland. The present study retrospectively analyzed data from the INSIGHT study to evaluate the incidence and clinical management of EGFR-positive NSCLC in Poland. The authors additionally aimed to identify predictors of the EGFR mutation and factors associated with clinical stage of the tumor at diagnosis. Incidence of EGFR mutations was 11.8% and the most common mutations were a deletion on exon 19 and an L858R substitution on exon 21. Mutations were strongly associated with female gender [male vs. female odds ratio (OR): 0.51; P=0.004] and never having smoked (current/past smoker vs. never smoked OR: 0.16; P<0.001), and advanced clinical stage (stage IV vs. stage I/II OR: 2.89; P=0.029). Patients with EGFR mutation were also observed to have a greater propensity to develop bone metastasis (OR: 11.62; P=0.008). Multivariate regression analysis demonstrated that patients with past or current smoking history or a poor performance on the Eastern Cooperative Oncology Group (ECOG) scale were less likely to have the EGFR mutation. Furthermore, EGFR-positive patients with greater ECOG scores and a tumor other than adenocarcinoma or squamous cell carcinoma were more likely to present advanced tumors. Early screening for EGFR mutation and the use of EGFR-targeting therapies as first-line agents may lead to better prognosis and successful clinical management of EGFR-positive NSCLC patients.

Real-world treatment patterns and survival outcomes for advanced non-small cell lung cancer in the pre-immunotherapy era in Portugal: a retrospective analysis from the I-O Optimise initiative

“…Of the patients at IPO-Porto with NSQ who were tested for EGFR or ALK mutations/rearrangements, 20.1 and 8.8%, respectively, were found to have mutations/rearrangements. These rates are comparable to those reported in several observational studies conducted in Portugal and elsewhere in Europe in which rates ranged from 10 to 28% for EGFR mutations [15][16][17][18][23][24][25][26][27], and from 3 to 12% for ALK rearrangements [17,24].…”

Prevalence of targeted therapy-related genetic variations in NSCLC and their relationship with clinicopathological characteristics

“…EGFR exon 19 deletion and L858R mutation were more commonly observed in female patients and adenocarcinoma. Similar observation has been reported between L858R mutation and gender, smoking, and histological type in a Japanese cohort [23] and a Polish cohort [24]. Further subgroup analysis confirmed the increased prevalence of those genetic variations in female patients in adenocarcinoma subgroup, and also in adenocarcinoma in male patients, which was not performed in previous studies.…”

“…Interestingly, after further standardization of smoking status, we found that in non-smokers, male patients were more likely to have squamous cell carcinoma and KRAS mutations and less likely to have EGFR L858R mutation than female patients. Previous study by Xue et al [26] and Ramlau et al [24] found that KRAS mutation was more common in male patients in a Chinese cohort, and EGFR L858R mutation was more common in female patients in the Polish cohort, but further standardization of smoking status was not performed in the study. Study by Stapelfeld et al [27] reported conflicting results that KRAS mutations were more frequently found in women than in men, possibly due to the different race of patients (Caucasian) investigated in that study.…”

WBP2 Downregulation Inhibits Proliferation by Blocking YAP Transcription and the EGFR/PI3K/Akt Signaling Pathway in Triple Negative Breast Cancer

“…Positive expression of EGFR is correlated with poor prognosis in several tumors, including TNBC [24,25]. EGFR overexpression has been detected in TNBC cell lines such as MDA-MB-231, BT-20, and HCC1937 [26].…”

“…Cell viability at different time points (24,48, 72 and 96 h) was evaluated by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) colorimetric assay. Briefly, 20 μl MTT solution (5 mg/mL; SigmaAldrich, St. Louis, Mo, USA) was added into each well, and cells were incubated at 37 °C for another 4 h. The reaction was terminated with 150 μL of dimethylsulfoxide (DMSO, Sigma-Aldrich) per well.…”