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

Abstract

Background 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. Methods 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. Results 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. Conclusion 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.

Osimertinib in uncommon EGFR exon 21 L861R and EGFR exon 18 deletion-insertion mutant non-small cell lung cancer—case report

“…Key studies, such as FLAURA which established osimertinib as first-line standard of care only included participants harbouring exon 19 deletion and L858R EGFR mutations ( 2 ). Both EGFR exon 21 L861R and EGFR exon 18 deletion-insertion are rare with an estimated prevalence of <1% and 0.3% respectively thus creating a challenge to determine whether these subtypes of EGFR mutations will respond to TKI therapy ( 3 , 4 ). There have been retrospective studies documenting benefit from osimertinib in subtypes of uncommon EGFR mutations and compound mutations, however there is limited published evidence of its efficacy in EGFR exon 21 L861R and EGFR exon 18 deletion-insertions ( 5 , 6 ).…”

The Importance of Screening for EGFR Mutation in Lung Cancer

“…This shows that lung cancer patients with stage 4 have higher mortality [3]. Stage 4 lung cancer patients are difficult to treat because the cancer has spread to other organs so it can only be treated to relieve the symptoms they are experiencing [4]. However, it turns out there is research that advanced lung cancer patients who have EGFR mutations can have hope of being treated as long as the type of mutation is properly detected.…”