Prevalence Of Epidermal Growth Factor Receptor Mutations Research Articles

Rapid and reliable testing for clinically actionable EGFR mutations in non-small cell lung cancer using the IdyllaTM platform: a real-world two-center experience in Greece

ABSTRACT Background Limited information exists on epidermal growth factor receptor (EGFR) molecular epidemiology in Greece. Next-generation sequencing (NGS) is the recommended method for EGFR genotyping in NSCLC. The Idylla Biocartis platform is a fully automated system for actionable EGFR mutation detection. Research design and methods We describe the prevalence of EGFR mutations in NSCLC patients in two high-volume clinical centers in Greece and compare key methods used for their determination. Eight hundred and fifty-seven FFPE samples from NSCLC patients were tested for EGFR mutations at University of Crete (UoC; n = 324) and at Evangelismos Hospital, Athens (Evangelismos; n = 503). Results The prevalence of EGFR mutations was 11.1% in the whole cohort (11.5% in non-squamous). The detection rate was 11.0% by NGS, 9.8% by Sanger and 11.3% by Idylla for the whole cohort (12.0% in non-squamous). The agreement between Idylla and Sanger was 93.2%. A targetable EGFR mutation was detected in 10.0% using tissue NGS alone, and in 16.0% using concurrent Idylla ctEGFR testing. Conclusion The frequency of EGFR mutations was as expected for a Caucasian population. The Idylla EGFR test performance is comparable to reference methods and with a shorter TAT. Adding a concurrent plasma Idylla test to tissue NGS testing increases the detection rate of EGFR mutations in NSCLC.

Molecular analysis of genetic mutations in non-small cell lung cancer in Morocco.

Non-small cell lung cancer (NSCLC) is a significant global health issue with diverse molecular profiles affecting treatment responses. Yet, NSCLC's molecular epidemiology in Morocco is largely unexplored. This study focuses on NSCLC genetic mutations, specifically in adenocarcinoma, among Moroccan patients to contribute to understanding NSCLC in this population. Ninety-four patients diagnosed with lung adenocarcinoma were analyzed. Formalin-fixed paraffin-embedded tissue samples were processed, and deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) was extracted using standardized protocols. Mutations were detected using the AmoyDx Pan Lung Cancer Polymerase Chain Reaction (PCR) Panel kit, and their frequencies were assessed through statistical analysis. Epidermal Growth Factor Receptor (EGFR) mutations were detected in 22.34% of patients, predominantly exon 19 deletions (66.66%) and exon 21 L858R mutations (23.80%). Anaplastic lymphoma kinase (ALK) gene fusion was observed in 3.19% of patients, and KRAS mutations in 1.06%. No mutations were found in other tested genes. A slightly higher mutation rate was noted in females (54.16%) compared to males (45.84%). The study reveals a distinct mutation profile in Moroccan NSCLC patients, with a notable prevalence of EGFR mutations, albeit lower than in some Asian populations. The significance of EGFR mutations in treatment response aligns with global findings, highlighting the importance of understanding regional molecular variations for personalized therapy. Despite limitations in sample size and clinical data, this study sheds light on the genetic landscape of NSCLC in Morocco. The observed mutation rates, particularly in EGFR, underscore the potential for targeted therapies in Moroccan NSCLC patients, emphasizing the need for further research to refine treatment strategies tailored to this population.

Genetic Alterations and Risk Factors for Recurrence in Patients with Non-Small Cell Lung Cancer Who Underwent Complete Surgical Resection

A definitive surgical resection is the preferred treatment for early-stage non-small cell lung cancer (NSCLC). Research on genetic alterations, including epidermal growth factor receptor (EGFR) mutations, in early-stage NSCLC remains insufficient. We investigated the prevalence of genetic alterations in early-stage NSCLC and the association between EGFR mutations and recurrence after a complete resection. Between January 2019 and December 2021, 659 patients with NSCLC who underwent curative surgical resections at a single regional cancer center in Korea were recruited. We retrospectively compared the clinical and pathological data between the recurrence and non-recurrence groups. Among the 659 enrolled cases, the median age was 65.86 years old and the most common histology was adenocarcinoma (74.5%), followed by squamous cell carcinoma (21.7%). The prevalence of EGFR mutations was 43% (194/451). Among them, L858R point mutations and exon 19 deletions were 52.3% and 42%, respectively. Anaplastic lymphoma kinase (ALK) rearrangement was found in 5.7% of patients (26/453) and ROS proto-oncogene 1 (ROS1) fusion was found in 1.6% (7/441). The recurrence rate for the entire population was 19.7%. In the multivariate analysis, the presence of EGFR mutations (hazard ratio (HR): 2.698; 95% CI: 1.458–4.993; p = 0.002), stage II (HR: 2.614; 95% CI: 1.29–5.295; p = 0.008) or III disease (HR: 9.537; 95% CI: 4.825–18.852; p < 0.001) (vs. stage I disease), and the presence of a pathologic solid type (HR: 2.598; 95% CI: 1.405–4.803; p = 0.002) were associated with recurrence. Among the recurrence group, 86.5% of the patients with EGFR mutations experienced distant metastases compared with only 66.7% of the wild type (p = 0.016), with no significant difference in median disease-free survival (52.21 months vs. not reached; p = 0.983). In conclusion, adjuvant or neoadjuvant targeted therapy could be considered more actively because EGFR mutations were identified as an independent risk factor for recurrence and were associated with systemic recurrence. Further studies on perioperative therapy for other genetic alterations are necessary.

EGFR Mutation Detection in Brazilian Patients With Non-Small-Cell Lung Cancer: Lessons From Real-World Data Scenario of Molecular Testing.

There is a paucity of consistent data concerning genetic mutations in Brazilian patients with lung cancer. The aim of this study was to retrospectively analyze epidermal growth factor receptor (EGFR) mutations detected in a real-world scenario using a large cohort of Brazilian patients with non-small-cell lung cancer (NSCLC). This was a cross-sectional, observational, descriptive study on the basis of a database of EGFR molecular analysis from tumor samples of patients with a confirmatory histopathological diagnosis of primary lung cancer. Specimens were collected from 2013 to 2017 and were tested using cobas, next-generation sequencing, and Sanger sequencing platforms. A total of 7,413 tumor specimens were tested. The patients were predominantly women with a median age of 67.0 years. Patients with at least one mutation represented 24.2% of the total sample. Among the positive patients, the majority had just one mutation, but two or more simultaneous mutations were observed in 1.52% of patients. Exon 19 deletion was the most prevalent alteration in the sample (12.8%), followed by exon 21 L858R (6.9%) and exon 20 insertion (1.6%). All others were considered uncommon mutations and were observed in 18.5% of all mutated patients and 4.0% of the total sample (2.3%-18.7% depending on the sequencing method). This study examined the prevalence of EGFR mutations in Brazilian patients with NSCLC using different technologies, suggesting that the type of method used, directed or nondirected against specific mutations, influences the analysis, particularly for uncommon mutations, which will be missed by mutation-specific approaches such as cobas testing. Our estimates are the largest in Latin America and are consistent with previous reports from other parts of the world. Besides the variability in methods described here as technology incorporation advances in a nonhomogeneous manner, it is probably like the real-world clinical setting Brazilian oncologists face in their daily practice.

Thyroid transcription factor 1 (TTF-1) negativity as a predictor of unfavorable response to EGFR-TKI therapy in advanced lung adenocarcinoma patients with EGFR mutations.

The absence of thyroid transcription factor 1 (TTF-1) is associated with a lower frequency of epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma (LUAD). The aim of this study was to assess the impact of TTF-1 expression on the clinical response to EGFR-tyrosine kinase inhibitor (TKI) treatment in patients with advanced LUAD. The data of patients with advanced LUAD who were admitted to the Beijing Tiantan Hospital and Peking University Cancer Hospital (China) between April 2009 and May 2023 was retrospectively analyzed. A total of 227 patients diagnosed with advanced LUAD were included, of which 28.2% (64/227) had TTF-1-negative adenocarcinoma, while 54.6% (124/227) harbored EGFR mutations. Negative TTF-1 expression significantly correlated with male sex (68.8% vs. 42.3%, p < 0.001), history of heavy smoking (57.8% vs. 36.2%, p = 0.003), poorly differentiated tumors (86.5% vs. 43.2%, p < 0.001), and lower frequency of EGFR mutations (26.6% vs. 65.6%, p < 0.001) compared with TTF-1 positivity. Multivariable logistic regression showed that low prevalence of EGFR mutations (p < 0.001) and male sex (p = 0.006) were independent predictive factors for the negative expression of TTF-1. Patients lacking TTF-1 also exhibited worse overall response rate (ORR; 23.5% vs. 54.2%, p = 0.019), disease control rate (DCR; 58.8% vs. 89.7%, p = 0.003), and median progression-free survival (PFS; 2.9 vs. 11.6 months, p < 0.001) following treatment with EGFR-TKIs compared to the TTF-1-positive patients with EGFR mutations. Patients with TTF-1-negative and EGFR-mutant LUAD show a diminished response to EGFR-TKIs.

The association between tyrosine kinase inhibitors and fatal arrhythmia in patients with non-small cell lung cancer in Taiwan.

As a standard therapy, tyrosine kinase inhibitors (TKIs) improved survival in patients with non-small cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutation. However, treatment-related cardiotoxicity, particularly arrhythmia, cannot be ignored. With the prevalence of EGFR mutations in Asian populations, the risk of arrhythmia among patients with NSCLC remains unclear. Using data from the Taiwanese National Health Insurance Research Database and NationalCancerRegistry, we identified patients with NSCLC from 2001 to 2014. Using Cox proportional hazards models, we analyzed outcomes of death and arrhythmia, including ventricular arrhythmia (VA), sudden cardiac death (SCD), and atrial fibrillation (AF). The follow-up duration was three years. In total, 3876 patients with NSCLC treated with TKIs were matched to 3876 patients treated with platinum analogues. After adjusting for age, sex, comorbidities, and anticancer and cardiovascular therapies, patients receiving TKIs had a significantly lower risk of death (adjusted HR: 0.767; CI: 0.729-0.807, p < 0.001) than those receiving platinum analogues. Given that approximately 80% of the studied population reached the endpoint of mortality, we also adjusted for mortality as a competing risk. Notably, we observed significantly increased risks of both VA (adjusted sHR: 2.328; CI: 1.592-3.404, p < 0.001) and SCD (adjusted sHR: 1.316; CI: 1.041-1.663, p = 0.022) among TKI users compared with platinum analogue users. Conversely, the risk of AF was similar between the two groups. In the subgroup analysis, the increasing risk of VA/SCD persisted regardless of sex and most cardiovascular comorbidities. Collectively, we highlighted a higher risk of VA/SCD in TKI users than in patients receiving platinum analogues. Further research is needed to validate these findings.

Advanced Non-small Cell Lung Cancer: EGFR Mutation Analysis Using Pyrosequencing and the Fully Automated qPCR-Based IdyllaTM System.

Epidermal growth factor receptor (EGFR) mutation status is of a major clinical significance in non-small cell lung cancer (NSCLC) management, as it guides therapeutic decision making to target patients for a better response to therapy. This implicates the introduction of EGFR mutation analysis as the standard of care for Moroccan NSCLC patients, which in itself entails the implementation of targeted methods for routine EGFR mutation analysis in our laboratories. In this study, we aimed to present 2 targeted methods for EGFR mutation identification and to determine the prevalence and spectrum of EGFR mutations in NSCLC Moroccan patients. A retrospective investigation of a cohort of 340 patients was undertaken to analyze somatic EGFR mutations in exons 18 to 21 using pyrosequencing and the IdyllaTM system. Of the enrolled patients, 70.9% were males and 29.1% were females. Predominately, 92% of cases had adenocarcinoma, and 53.7% of patients self-reported a history of smoking. Overall, 73 patients (21.7%) harbored an EGFR mutation, the most prevalent of which were the exon 19 deletions (53.4%) followed by exon 21 substitutions (31%). Exon 18 mutations and exon 20 alterations occurred in 8.1% and 6.7% of the positive EGFR mutation cases, respectively. Of the analyzed cases, all of the EGFR-mutated patients had adenocarcinoma. EGFR mutation prevalence was significantly higher in females (females vs males: 38.4% vs 14.5%, P < .001) and non-smokers (non-smokers vs non-smokers: 36% vs 10.3%, P < .001). The featured pyrosequencing and the IdyllaTM system are targeted methods endowed with high sensitivity and specificity as well as other compelling characteristics which make them great options for routine EGFR mutation testing for advanced NSCLC patients. These findings underline the imperious need for implementing quick and efficient targeted methods for routine EGFR mutation testing among NSCLC patients, which is particularly useful in determining patients who are more likely to benefit from targeted therapy.

Predicting EGFR mutational status from pathology images using a real-world dataset

Treatment of non-small cell lung cancer is increasingly biomarker driven with multiple genomic alterations, including those in the epidermal growth factor receptor (EGFR) gene, that benefit from targeted therapies. We developed a set of algorithms to assess EGFR status and morphology using a real-world advanced lung adenocarcinoma cohort of 2099 patients with hematoxylin and eosin (H&E) images exhibiting high morphological diversity and low tumor content relative to public datasets. The best performing EGFR algorithm was attention-based and achieved an area under the curve (AUC) of 0.870, a negative predictive value (NPV) of 0.954 and a positive predictive value (PPV) of 0.410 in a validation cohort reflecting the 15% prevalence of EGFR mutations in lung adenocarcinoma. The attention model outperformed a heuristic-based model focused exclusively on tumor regions, and we show that although the attention model also extracts signal primarily from tumor morphology, it extracts additional signal from non-tumor tissue regions. Further analysis of high-attention regions by pathologists showed associations of predicted EGFR negativity with solid growth patterns and higher peritumoral immune presence. This algorithm highlights the potential of deep learning tools to provide instantaneous rule-out screening for biomarker alterations and may help prioritize the use of scarce tissue for biomarker testing.

Significance of Immunohistochemistry Testing in the Diagnosis and Subtyping of Lung Carcinomas- A Retrospective Study from a Tertiary Care Centre in Southern Rajasthan

Introduction: In the present era, the classification of lung carcinoma is not confined to Small Cell Lung Carcinoma (SCLC) and Non Small Cell Lung Carcinoma (NSCLC). Precise subtyping of lung carcinoma has a direct impact on patient management and prognosis. Further molecular study helps in identifying adenocarcinoma receptors, such as Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK), which are useful in targeted therapy. Aim: To assess the role of Immunohistochemistry (IHC) in accurate diagnosis and subtyping of lung carcinoma and to analyse the prevalence of EGFR mutations and ALK rearrangement in lung adenocarcinoma. Materials and Methods: A retrospective hospital-based, observational study was conducted at the Department of Pathology of American International Institute of Medical Sciences, Udaipur, Rajasthan from January 2020 to August 2021. Total of 105 cases of guided core needle biopsies from lung and bronchoscopic biopsies were included. IHC markers were applied based on histopathological diagnosis from a panel of p63, Cytokeratin 7 (CK7), AE1/AE3, Thyroid Transcription Factor (TTF1), Napsin A, p40, synaptophysin, chromogranin, CD56 and Ki67. Adenocarcinoma cases were further analysed for EGFR mutations and ALK rearrangements. Data was tabulated and analysed statistically using Microsoft Excel to determine the percentage frequency distribution of cases. Results: Among 105, there were 88 males and 17 females and the mean age of the population was 60.57 years. The most prevalent subtype of lung malignancy was squamous cell carcinoma (44.7%) followed by adenocarcinoma (29.5%). The diagnostic accuracy of squamous cell carcinomas and adenocarcinomas on morphology was 93.1% and 84.6%, respectively and for small cell carcinoma it was 100%. Amongst 28 cases of adenocarcinoma, EGFR mutation was found in 46.42% cases whereas ALK mutation was found only in 21.42% cases. Conclusion: The study highlights the importance of IHC, and a substantial prevalence of EGFR mutations was found in patients with lung carcinoma.

Determination of EGFR Mutation Prevalence in Advanced and Metastatic Lung Squamous Cell Carcinoma in Vietnam

Abstract: This paper aims to determine the rate of epidermal growth factor receptor (EGFR) gene mutations in advanced and metastatic squamous cell lung cancer in Vietnamese patients. EGFR mutation testing was performed on 559 formalin-fixed paraffin-embedded tissue samples from advanced and metastatic squamous cell lung cancer patients by real-time PCR. The results showed that EGFR mutations were found in 8.4%. Most of them were exon 19 deletions, approximately 51.1%. Multivariate analysis showed that EGFR mutations were more prevalent in gender (p&lt;0.0001). In conclusion, EGFR mutation testing should be performed in patients with squamous cell lung cancer.&#x0D; Keywords: Lung squamous cell carcinoma, EGFR gene. &#x0D; &#x0D;

Evaluating Real World Mutational Differences Between Hispanics and Asians in NSCLC at a Large Academic Institution in Los Angeles

IntroductionHispanics living in the United States have higher rates of Epidermal Growth Factor Receptor (EGFR) mutations compared with Non-Hispanic Whites. While this higher incidence is like Asian patients living in the United States, the outcomes for Hispanic patients differ. We looked to compare the variances in mutational profiles between Hispanics and Asians in Los Angeles. Patients and MethodsThree hundred ninety three non-small cell lung cancer (NSCLC) patients treated at Los Angeles County + University of Southern California (LAC + USC) Medical Center and Norris Comprehensive Cancer Center who received comprehensive genomic profiling (CGP) were evaluated from July 2017 to August 2020. CGP was done using tissue biopsies (n = 211) from Caris Life Sciences and liquid biopsies (n = 231) from Guardant Health. Multivariate logistic regression evaluated the role of race between Hispanics and Asians. ResultsIn the Hispanic cohort (n = 90), 50.0% were male, median age of diagnosis was 62, 54.5% were non-smokers, and 85.5% had adenocarcinoma. In Asians (n = 142), 47.5% were male, median age of diagnosis was 65, 59.6% were non-smokers, and 83.8% had adenocarcinoma. Hispanic patients had greater prevalence of Kirsten rat sarcoma virus (KRAS) mutations (odds ratio [OR] 4.42, 95% confidence interval [95% CI]: 1.63-12.83) and lesser prevalence of EGFR mutations (OR 0.31, 95% CI: 0.16-0.59). There were a greater proportion of Hispanic smokers with KRAS mutations (14/41; 34.1%) than Asian smokers (4/58; 6.9%). ConclusionWe saw a greater percentage of Hispanics with KRAS mutations despite similar smoking percentages along with a greater percentage of Asians with EGFR mutations. This study shows that ethnic and racial backgrounds of the patient can influence the effects of potentially carcinogenic exposures leading to variances of mutation frequency of NSCLC among different ethnicities.

Frequency of Epidermal Growth Factor Receptor Mutations among Iraqi Non-small Cell Lung Cancer Patients

Background: Epidermal Growth Factor Receptor (EGFR) mutations are actually currently utilized as genetic biomarkers for focused lung carcinoma treatment. Unfortunately, there is minimal data on Iraq’s proportion of mutations in EGFR gene. The current study’s objective is to find the mutations prevalence of EGFR gene mutations and the dominant EGFR mutations in patients with lung carcinoma type non-small cell (NSCLC) from Iraq. Methods: On tissues taken from paraffin-embedded blocks of NSCLC patients, RT-PCR was performed to investigate the mutations in EGFR gene. Results: This study involved 234 paraffin tissue blocks of NSCLC patients in addition to17 paraffin tissue blocks with invalid results, although it was tested more than three times. This study was used Polymerase chain reaction (PCR) technique to determine mutations in EGFR gene. Forty-seven out of 234 patients had an EGFR mutation (20%). The most prevalent anomaly found in exon19 Del (70.3%) followed by L 858 R (15%). High mutations were found among two age groups (60–69) and 70–79 which suggest increased mutation among old ages when compared with young people. However, no significant difference between EGFR mutation status and sex or age status was found. Conclusion: The prevalence of EGFR mutation among Iraqi patients is 20% which is compatible with a percentage of cases documented in Asian populations and the most prevalent EGFR mutant in Iraq cases is the EX19del.

EGFR mutations in lung carcinomas: Mutation profile and survival analysis.

e20518 Background: Epidermal growth factor receptor (EGFR) mutation have been demonstrated to be both predictive and prognostic for patients with metastatic lung cancer. The administration of EGFR tyrosine kinase inhibitors (TKIs) has improved survival in this group of patients. Several generations of EGFR TKIs are currently available. The EGFR mutations have been divided into common and rare. The common mutations include Exon 19 deletion and Exon 21 L858R mutations and rest are grouped as rare. The presence of visceral metastasis in the brain and liver are usually portends a poor prognosis. Methods: We conducted a retrospective analysis of lung cancer patients who attended our hospital outpatient department from 2017 to 2021. The prevalence, demographics and clinical profile of EGFR common and rare mutations were studied using descriptive statistics. Survival of EGFR mutated patients was plotted using Kaplan Meier plots. SPSS was used for statistical analysis. Results: The prevalence of EGFR mutation among metastatic lung cancer was 14.10% (161/1148). The median age of the group was 60 years (23- 104 years). Smokers with EGFR mutations were 11.8% (n = 19). Male to Female ratios was 76:85 (47.2% and 52.8%). Three patients with squamous cell carcinoma exhibited EGFR mutation. Most common EGFR TKI used was Gefitnib. Osimertinib was used in 13 patients (1.4%). The percentage of common mutations were 85.75% (N = 132) and rare mutations were 14.3% (n = 22). The type of mutations could not be identified in 10 patients. The percentage of patients with exon 19 deletion were 63% (n = 97) and L858R were 24.7% (n = 38). Visceral metastasis (brain and liver) was seen in 47 patients (n = 29.2%). Brain progression was seen in 32 patients (n = 19.9%). The survival of patients with EGFR exon 19 deletion and L858R mutation was 16.36 + 8.97 months and 15.97+ 10.93 months, Survival among patients with common mutation was 16.20 + 9.57 months and among rare mutation was 13.43 + 12.19 months. Median Survival period of patients with visceral metastasis was 12 months (0 to 38 months). Conclusions: In our retrospective study, there was no significant difference between survival among common and rare EGFR mutations.

59P Clinical utility of plasma cell-free DNA EGFR mutation analysis in treatment-naïve stage IV non-small cell lung cancer patients

Plasma cell-free DNA epidermal growth factor receptor (EGFR) mutation tests are widely used at initial diagnosis and at progression in stage IV non-small cell lung cancer (NSCLC). We analyzed the factors associated with plasma EGFR mutation detection and the effect of plasma EGFR genotyping on the clinical outcomes of the patients with treatment-naïve stage IV NSCLC. In this retrospective cohort study, we included subjects with treatment-naïve stage IV NSCLC who underwent plasma EGFR genotyping between 2018 and 2020. The presence of plasma EGFR mutation was determined by real-time polymeric chain reaction. The prevalence of EGFR mutation in this cohort was 52.7% (164/311). Among 164 EGFR mutant subjects, 34 (20.7%) were positive for the plasma EGFR mutation assay only. The diagnostic sensitivity of the plasma EGFR mutation assay (80.5%) was similar to that of the tissue EGFR mutation assay (79.3%, p = 0.787). In multivariable analysis, the detection of plasma EGFR mutation was significantly related to higher serum carcinoembryonic antigen levels, never-smoker status, N3 stage, and brain or intrathoracic metastasis. The time to treatment initiation (TTI) of the plasma EGFR mutation-positive group (14 days) was shorter than that of the plasma EGFR mutation-negative group (21 days, p < 0.001). More patients received the 1st line EGFR-TKI in the plasma positive group compared with the tissue positive group. Smoking status and the factors reflecting tumor burden were associated with detection of plasma EGFR mutation. The plasma EGFR mutation assay can shorten the TTI, and facilitate the 1st line EGFR-TKI therapy for patients with treatment-naïve stage IV NSCLC, especially in the region of high-prevalence of EGFR mutation.

Clinical Utility of Plasma Cell-Free DNA EGFR Mutation Analysis in Treatment-Naïve Stage IV Non-Small Cell Lung Cancer Patients.

Background: Plasma cell-free Deoxyribo nucleic acid epidermal growth factor receptor (EGFR) mutation tests are widely used at initial diagnosis and at progression in stage IV non-small cell lung cancer (NSCLC). We analyzed the factors associated with plasma EGFR mutation detection and the effect of plasma EGFR genotyping on the clinical outcomes of the patients with treatment-naïve stage IV NSCLC. Methods: In this retrospective cohort study, we included subjects with treatment-naïve stage IV NSCLC who underwent plasma EGFR genotyping between 2018 and 2020. The presence of plasma EGFR mutation was determined by real-time polymeric chain reaction. Results: The prevalence of EGFR mutation in this cohort was 52.7% (164/311). Among 164 EGFR mutant subjects, 34 (20.7%) were positive for the plasma EGFR mutation assay only. In multivariable analysis, the detection of plasma EGFR mutation was significantly related to higher serum carcinoembryonic antigen levels, never-smoker status, N3 stage, and brain or intrathoracic metastasis. The time to treatment initiation (TTI) of the plasma EGFR mutation-positive group (14 days) was shorter than that of the plasma EGFR mutation-negative group (21 days, p < 0.001). More patients received the 1st line EGFR-TKI in the plasma positive group compared with the tissue positive group. Conclusion: Smoking status and the factors reflecting tumor burden were associated with the detection of plasma EGFR mutation. The plasma EGFR mutation assay can shorten the TTI, and facilitate the 1st line EGFR-TKI therapy for patients with treatment-naïve stage IV NSCLC, especially in the region of high-prevalence of EGFR mutation.

Prevalence and Patterns of EGFR Mutations in Non-small Cell Lung Cancer in the Middle East and North Africa

ObjectivesThis study aims to analyze the prevalence and spectrum of epidermal growth factor receptor (EGFR) mutations within the Middle East and North Africa region, compare the findings to other parts of the world, and explore the geographic disparities of EGFR mutations across the region.MethodsWe conducted a literature search using the terms “[EGFR] AND [mutation] AND [Non-Small Cell Lung Cancer] AND [Middle East OR North Africa]”, using PubMed, Science Direct, Web of science, Embase, Scopus, and Google scholar.ResultsA total of 15 eligible studies were included and 6122 patients with non-small cell lung cancer (NSCLC) were analyzed. Male patients were predominant in all of the considered studies, accounting for 70.4%. Of the included patients, 65.6% were smokers and 88.3% had been diagnosed with adenocarcinoma. Overall, EGFR mutations prevalence was 17.2%. In the Middle East, the reported frequency was 16.5%, ranging from 11.3% in Lebanon to 29.7% in the Gulf region. In North Africa, the prevalence of EGFR mutations was 18%, ranging from 17.5% in Egypt to 21.5% in Morocco. The most prevalent mutations were the exon 19 deletions (46.7%) followed by exon 21 substitutions (31.1%). Exon 20 alterations were detected in 10.8% of the analyzed cases, whereas exon 18 mutations were reported in 3.4% of the EGFR-mutated patients. There was 1.1% of patients that had concurrent EGFR mutations. Overall, EGFR mutation prevalence was higher in females [females vs males: 29.7% vs 5.9%, P<.001], non-smokers [non-smokers vs smokers: 31.3% vs 9.6%, P<.001], and patients with adenocarcinoma [adenocarcinoma vs non-adenocarcinoma: 18.8% vs 6.5%, P<.001].ConclusionEGFR mutation prevalence among the Middle East and North Africa populations is slightly higher than that seen in NSCLC patients of Caucasian ethnicity but is lower than that identified in Asian NSCLC patients. The distribution of these mutations varies considerably throughout the region.

EGFR-mutation testing and TKI treatment patterns in locally advanced and metastatic NSCLC in Norway – A nationwide retrospective cohort study

BackgroundTesting for epidermal growth factor receptor mutation (EGFRm) status is a prerequisite to identify eligible patients for tyrosine kinase inhibitors (TKI) treatment. However, EGFR testing of patients with non-small cell lung cancer (NSCLC) is suboptimal in many parts of the world. The aim of this study was to describe real-world EGFR testing practice, EGFRm prevalence, and subsequent TKI treatment patterns in Norway. Patients and methodsThis retrospective, observational, cohort study included all incident locally advanced and metastatic non-squamous NSCLC patients registered in the Norwegian Cancer Registry during 2010–2017. A cohort with follow-up through 2018 was formed with linkage to nationwide registries on comorbidities, prescribed drugs and causes-of-death. ResultsA total of 10,717 patients were included, of which 35% (3782) with locally advanced NSCLC and 65% (6935) with metastatic disease. Mean age at diagnosis was 71 years and 47% were female. EGFR testing among patients with metastatic NSCLC increased from 41% to >64% between 2010 and 2017, with a relative stable incidence of EGFRm+ (∼9%). More than 85% of EGFRm+ patients received TKI treatment. Patients with the most dismal prognosis (>80 age, comorbidities) and with diagnosis based on cytology/imaging were less likely to be tested. Differences in testing were observed between regions. ConclusionDespite increased test rates over the study period, in Norway, a significant proportion of patients with non-squamous metastatic NSCLC are still not tested for EGFR. To maximize the identification of eligible patients for targeted therapies, increased testing is recommended, regardless of age, comorbidity rate and place of residence.

Worldwide Prevalence of Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer: A Meta-Analysis.

BackgroundIdentification of variable epidermal growth factor receptor (EGFR) gene mutations in non-small cell lung cancer (NSCLC) is important for the selection of appropriate targeted therapies. This meta-analysis was conducted to provide a worldwide overview of EGFR mutation and submutation (specifically exon 19 deletions, exon 21 L858R substitutions, and others) prevalence, and identify important covariates that influence EGFR mutation status in patients with advanced NSCLC to address this clinical data gap.MethodsEmbase® and MEDLINE® in Ovid were searched for studies published between 2004 and 2019 with cohorts of ≥ 50 adults with EGFR mutations, focusing on stage III/IV NSCLC (≤ 20% of patients with stage I/II NSCLC). Linear mixed-effects models were fitted to EGFR mutation endpoints using logistic transformation (logit), assuming a binomial distribution. The model included terms for an intercept reflecting European studies and further additive terms for other continents. EGFR submutations examined were exon 19 deletions, exon 21 L858R substitutions, and others.ResultsOf 3969 abstracts screened, 57 studies were included in the overall EGFR mutation analysis and 74 were included in the submutation analysis relative to the overall EGFR mutation population (Europe, n = 12; Asia, n = 51; North America, n = 5; Central America, n = 1; South America, n = 1; Oceania, n = 1; Global, n = 3). The final overall EGFR mutations model estimated Asian and European prevalence of 49.1% and 12.8%, respectively, and included an additive covariate for the proportion of male patients in a study. There were no significant covariates in the submutation analyses. Most submutations were actionable: exon 19 deletions (49.2% [Asia]; 48.4% [Europe]); exon 21 L858R substitutions (41.1% [Asia]; 29.9% [Europe]).ConclusionsAlthough EGFR mutation prevalence was higher in Asian than Western countries, data support worldwide testing for EGFR overall and submutations to inform appropriate targeted treatment decisions.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40291-021-00563-1.

Driver gene alterations in lung adenocarcinoma: Demographic features of 2544 Chinese cases.

To understand the association between driver gene variations and age and gender in patients with lung adenocarcinoma, we investigated mutations of the three most important driver genes-epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) fusion genes and c-ros oncogene 1 (ROS1)-in this retrospective cohort study. Patients newly diagnosed with lung adenocarcinoma who received EGFR and ALK/ROS1 gene tests at our hospital from September 2014 to May 2019 were enrolled. EGFR mutations and ROS1 fusions were examined by ARMS-PCR and ALK fusions by Ventana-D5F3 IHC assay and ARMS-PCR. Of 2544 eligible subjects, 2539 accomplished EGFR mutation tests. The prevalence of EGFR mutations was 62.1% in females, higher than that of 45.1% in males. In females, the EGFR mutation rate remained relatively stable at 60%-65% across the six age groups. Females showed an increased distribution of EGFR L858R and a decreased distribution of exon 19 deletion (19Del) by age. The incidence of ALK/ROS-1 rearrangements decreased significantly with age. EGFR 19Del mutation is more prevalent in younger males and females, while L858R mutation is prevalent in older females. Both ALK and ROS1 rearrangements are more common in younger lung adenocarcinoma. The young lung adenocarcinoma population is a distinct group rich in targetable genomic alterations, and more research is needed to understand the mechanism.

Epidermal growth factor receptor mutations in non-small cell lung cancer undetected by high-sensitivity allele-specific real-time polymerase chain reaction-based assays.

Identifying epidermal growth factor receptor (EGFR) mutation status is critical for planning lung cancer treatment. Sanger sequencing detects both known and novel mutations but shows poor sensitivity. High-sensitivity allele-specific real-time polymerase chain reaction (ASRP)-based assays offer quick and reliable results, but may overlook uncommon mutations. We aimed to define the rate at which high-sensitivity ASRP-based assays missed uncommon EGFR mutations. Non-small cell lung cancer specimens that were diagnosed as EGFR wild-type (EGFR-WT) by high-sensitivity ASRP-based assays and had residual DNA samples were sent for Sanger sequencing. Patient characteristics and clinical features were evaluated by chart review, and outcomes of EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy were studied. Hundred DNA specimens diagnosed by high-sensitivity ASRP-based assays as EGFR-WT were rechecked by Sanger sequencing. Two samples which were re-biopsy specimens from patients with EGFR mutations were excluded from the analysis. Sanger sequencing was failed in 24 samples. Among the remaining 74 samples, 6 (8.1%) had EGFR mutations-one exhibited exon 19 deletion (delT751_I759insS), two exhibited substitution mutations (S768I+V769L and L861Q), and three exhibited exon 20 insertions (N771_P772insN, P772_H773insHP, and H773_V774insAH). Only the patient with the exon 19 deletion had received EGFR-TKI therapy. Although the best tumor response was only stable disease, this was maintained for >10 months. High-sensitivity ASRP-based assays can overlook uncommon mutations. This detection failure rate is worth noting, especially when treating patients from regions known to have a high prevalence of EGFR mutation. Patients carrying uncommon mutations may still benefit from EGFR-TKI therapy.