Antitumor activity of aumolertinib, a third-generation EGFR tyrosine kinase inhibitor, in non-small-cell lung cancer harboring uncommon EGFR mutations

Uncommon epidermal growth factor receptor (EGFR) mutations account for 10%-20% of all EGFR mutations in non-small-cell lung cancer (NSCLC). The uncommon EGFR-mutated NSCLC is associated with poor clinical outcomes and generally achieved unsatisfactory effects to the current therapies using standard EGFR-tyrosine kinase inhibitors (TKIs), including afatinib and osimertinib. Therefore, it is necessary to develop more novel EGFR-TKIs to treat uncommon EGFR-mutated NSCLC. Aumolertinib is a third-generation EGFR-TKI approved in China for treating advanced NSCLC with common EGFR mutations. However, it remains unclear whether aumolertinib is effective in uncommon EGFR-mutated NSCLC. In this work, the in vitro anticancer activity of aumolertinib was investigated in engineered Ba/F3 cells and patient-derived cells bearing diverse uncommon EGFR mutations. Aumolertinib was shown to be more potent in inhibiting the viability of various uncommon EGFR-mutated cell lines than those with wild-type EGFR. And in vivo, aumolertinib could also significantly inhibit tumor growth in two mouse allograft models (V769-D770insASV and L861Q mutations) and a patient-derived xenografts model (H773-V774insNPH mutation). Importantly, aumolertinib exerts responses against tumors in advanced NSCLC patients with uncommon EGFR mutations. These results suggest that aumolertinib has the potential as a promising therapeutic candidate for the treatment of uncommon EGFR-mutated NSCLC.

ALK, ROS1 and EGFR status of lung cancers in the Aegean Region of Turkey

Background/Aims: As targeted therapies are promising in the treatment of lung cancer (LC), it is important to identify the genetic variations in tumors. The present research aimed to determine the regional prevalence of alterations in ALK, ROS1, and EGFR genes. Materials and Methods: ALK rearrangement in 1152, ROS1 rearrangement in 390, and EGFR mutations in 1054 cases with LC were evaluated. Results: Alteration rates of ALK, ROS1, and epidermal growth factor receptor (EGFR) genes were 3.5%, 0.4%, and 11.2% in the samples, respectively. ALK rearrangements were mainly detected in young patients (P < 0.01) and in females (P < 0.01). Females were also more often inflicted by EGFR variations, especially from the exon 19 deletion. Exon 21 L858R mutations were more frequently found in men. However, any statistical significance between EGFR alterations and gender or age was not discovered. Conclusion: In this study, molecular changes were less frequent than expected. We thought that this low rate confirmed the aphorism of “smokes like a Turk, ” which could be because almost all patients were active or passive smokers.

Epidermal growth factor receptor mutations in adenocarcinoma lung: Comparison of techniques for mutation detection

Background: Targeted therapy using tyrosine kinase inhibitors in cases of non-small-cell lung carcinoma (NSCLC) that harbor epidermal growth factor receptor (EGFR) mutations has drastically improved the overall survival rate. The current study estimated the frequency of EGFR mutations in the Indian population by analyzing the diagnostic parameters of various techniques available for the detection of these mutations. Materials and Methods: A case series of 100 histologically diagnosed and immunohistochemically confirmed NSCLC with the adenocarcinoma phenotype comprises the study sample. EGFR mutations were detected using clone-specific immunohistochemistry (IHC), real-time polymerase chain reaction (PCR), and Sanger sequencing. Results: EGFR mutations were identified in 48% cases with 72.78% mutations involving exon 19. Clone-specific IHC had a low sensitivity of 46.43%, and the specificity was 79.17%. Sanger sequencing yielded interpretable results in 16% cases only, which were in concordance with the results of real-time PCR. Conclusion: EGFR mutations are increasingly being explored for targeted therapy and personalized medicine. Real-time PCR was found to be the best and the most accurate method for the detection of somatic EGFR mutations in adenocarcinoma primarily in the lungs.

Lung Adenocarcinomas with Pulmonary Miliary Metastases: A Case Report and Literature Review / 中国肺癌杂志

BACKGROUND@#Lung adenocarcinoma with miliary metastasis in both lungs is easily misdiagnosed. The aim of this study is to investigate the clinical features of lung adenocarcinoma with miliary metastases in both lungs and to improve the clinician's understanding of the disease.@*METHODS@#The clinical manifestation, radiology and pathology were analyzed in one patient with miliary intrapulmonary carcinomatosis in Affiliated Hospital of Zunyi Medical University. A review of literature was performed with "miliary intrapulmonary carcinomatosis", "lung cancer miliary", "pulmonary nodule, lung cancer" and "EGFR miliary" as key words in PubMed, Wangfang datebase and CNKI.@*RESULTS@#The patient was a 52 year-old woman with a history of productive cough for 2 months, which aggraveted with shortness of breath for 1 month. Her computed tomography of chest showed diffuse military nodules distributed at bilateral lungs. Computed tomography (CT)-guided needle biopsy of the left lung revealed lung adenocarcinoma and epidermal growth factor receptor (EGFR) exon 21 L858R mutation. The patient was treated with gefitinib 250 mg per day. The chest CT was reviewed several times during this period, which shows the double lung nodules were reduced. The patient is generally in good condition and her symptoms have improved. By literature review, we found relevant 7 Chinese articles and 56 English articles, a total of 16 cases have been reported. 17 patients were lung adenocarcinoma, 2 patients did not describe whether to detect EGFR gene mutations, 1 patient did not have EGFR gene mutation; 10 patients were EGFR exon 19 deletion, 1 patient was ALK positive, 1 patient was EGFR exon 21L858R mutation, 2 patients were EGFR exon 20 insertion.@*CONCLUSIONS@#Lung adenocarcinoma with miliary metastasis in both lungs is a rare phenomenon. We should pay attention to the performance to avoid misdiagnosis. Most of the adenocarcinoma subtypes have EGFR mutations, and EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are the preferred treatment choice for this type of patients.

Chemotherapy drugs affect terminal lung cancer EGFR mutation status / 中国基层医药

Objective To compare the advanced non -small cell lung cancer (NSCLC)patients before and after chemotherapy peripheral blood EGFR mutation status,we understand whether the chemotherapy drug impacts the EGFR mutation status of the advanced NSCLC patients,so as to improve the precision of EGFR TKIs -drug use. Methods To collect the peripheral blood of 30 cases of advanced NSCLC before chemotherapy and after chemotherapy for 6 cycles.DHPLC technique was used to detect the EGFR mutation states of EGFR exon 19 and in exon 21.Results In 30 patients,chemotherapy prior EGFR mutation positive rate was 53.3% (16 /30).After 6 cycles of chemotherapy, the EGFR mutation positive rate was 36.6% (11 /30),the consistent rate was 56.6 (17 /30)before and after chemo-therapy,inconsistent rate was 53.4% (13 /30).10 cases from positive to negative before chemotherapy,3 cases from negative into positive before chemotherapy with statistical significance (P =0.046).Six EGFR19 exons changed, change rate of 20%,8 EGFR21 exons shift changed at a rate of 26%.EGFR19,21 shift in 1 case,with no statistical significance(P =0.39,P >0.05).Conclusion (1)The late NSCLC patients before and after peripheral blood of EGFR mutation status change,so before starting the targeted therapy we must recive real -time detection of peripheral blood EGFR mutation status,so as to decide whether to choose EGFR TKIs targeted drug therapy.(2)EGFR21 exons transformation rate is higher than EGFR19 exons conversion rate,but with no statistical difference,this phenomenon may be related to EGFR19 exons patients who with EGFR mutations -TKIs treatment efficiency is higher.