scholarly journals Detecting EGFR mutations in patients with non-small cell lung cancer

2018 ◽  
Vol 21 (1) ◽  
pp. 13-17 ◽  
Author(s):  
ZA Hammoudeh ◽  
O Antonova ◽  
R Staneva ◽  
D Nikolova ◽  
Y Kyuchukov ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Smoking Status ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Histological Types ◽  
Egfr Tkis

Abstract Mutations in the receptor of the epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) are used as biomarkers for predicting the response of treatment with EGFR tyrosine kinase inhibitors (EGFR TKIs). Non-small cell lung cancer patients usually have activating EGFR mutations that leads to a very good response when they are treated with EGFR TKIs. Our tumor samples were examined for the presence of sensitive mutations in the EGFR gene, resistant mutations or the absence of mutations. To identify the types of the mutation, we used a real-time polymerase chain reaction (RT-PCR) method. Additionally, we evaluated the frequency of EGFR mutations and their association with smoking status, gender and histology. The tumor samples (n = 551) were tested for 29 somatic mutations in the EGFR gene. Sensitive mutations in the EGFR genes were found in 55 NSCLC samples (10.0%). The prevalence of EGFR mutations was much higher for females than for males (27.1 vs. 3.9%, p <0.001). The prevalence of EGFR mutations was greater in subjects who had never smoked than in smokers (15.0 vs. 6.08%, p <0.003). Additionally, the frequency of EGFR mutations was higher in adenocarcinomas than in other histological types (14.9 vs. 5.1%; p <0.001). Our results show that activating mutations on the EGFR gene are more frequent in females than in males, in adenocarcinoma than other histological types and in non smokers than smokers.

Immunotherapy in advanced non-small-cell lung cancer with EGFR mutations

Immunotherapy ◽  
2020 ◽  
Vol 12 (16) ◽  
pp. 1195-1207
Author(s):  
Fangfang Liu ◽  
Xun Yuan ◽  
Jizong Jiang ◽  
Qian Chu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Egfr Tkis

EGFR-tyrosine kinase inhibitors (EGFR-TKIs) had been regarded as the front-line treatment for advanced non-small-cell lung cancer (NSCLC) patients with EGFR mutations. However, resistance to EGFR-TKIs is inevitable, it remains a major challenge. Immune checkpoint inhibitors (ICIs) had shown superior clinical efficacy in many types of solid tumors, while it exhibited impaired overall efficacy in NSCLC with  EGFR mutations. In this review, we will perform a meta-analysis to assess the relationship between the programmed death ligand 1 (PD-L1) expression and clinical benefit of EGFR-TKIs. We also overview the immunotherapy in advanced NSCLC patients with EGFR mutations to investigate the potential biomarkers predicting the ICIs efficiency, and the subgroups that could benefit from ICIs treatment.

Response with pemrbolizumab in a patient with EGFR mutated non-small cell lung cancer harbouring insertion mutations in V834L and L858R

2021 ◽  
pp. 107815522110578
Author(s):  
Matthew J. Hadfield ◽  
Alla Turshudzhyan ◽  
Khalid Shalaby ◽  
Aswanth Reddy
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Durable Response ◽  
Egfr Mutated

Introduction Lung cancer is the leading cause of cancer-related deaths with non-small cell lung cancer (NSCLC) being the most common of them. About a third of NSCLC cases have an epidermal growth factor (EGFR) mutation, which is usually susceptible to tyrosine kinase inhibitors (TKIs). In rare cases where patients progress through TKI therapy, the use of immune checkpoint inhibitors (ICIs) remains controversial. Case report We describe a case of a patient with significant history of smoking and EGFR mutated programmed death ligand-1 (PD-L1) positive NSCLC who was initially treated with TKI therapy. Management/Outcome While patient progressed on TKI therapy, he was able to achieve a durable response with a single PD-L1 agent, pembrolizumab. Contrary to the available evidence, the presented EGFR mutant NSCLC responded to PD-L1 pathway inhibition. Discussion From our observation Pembrolizumab could be promising in patients with rare EGFR mutations who do not respond to EGFR directed therapy. Our report provides supporting data for the use of immunotherapies in patients with EGFR mutated NSCLC.

scholarly journals Clinical Characteristics of Osimertinib Responder in Non-Small Cell Lung Cancer Patients with EGFR-T790M Mutation

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 365 ◽  
Author(s):  
Akihiro Yoshimura ◽  
Tadaaki Yamada ◽  
Naoko Okura ◽  
Takayuki Takeda ◽  
Kazuki Hirose ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Nsclc Patients ◽  
Egfr T790m ◽  
Egfr Tkis

Osimertinib is a mutant-selective EGFR inhibitor that is effective against non-small cell lung cancer (NSCLC) in patients with the EGFR-T790M mutation, who are resistant to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, the factors affecting response to osimertinib treatment are unknown. In this retrospective study, 27 NSCLC patients with the EGFR-T790M mutation were enrolled at five institutions in Japan. Among several parameters tested, the progression-free survival (PFS) associated with the initial EGFR-TKIs was positively correlated with the PFS after osimertinib treatment (p = 0.021). The median PFS following osimertinib treatment and the overall survival (OS) were longer in patients who responded to osimertinib than in those who did not (17.7 months versus 3.5 months, p = 0.009 and 24.2 months versus 13.5 months, p = 0.021, respectively). A multivariate analysis demonstrated that the PFS with initial EGFR-TKIs was significantly related to the PFS with osimertinib treatment (p = 0.035), whereas osimertinib response was significantly related to the PFS and OS with osimertinib treatment (p = 0.016 and p = 0.006, respectively). Our retrospective observations indicate that PFS following the initial EGFR-TKI treatment and the response rate to osimertinib might be promising predictors for effective osimertinib treatment in NSCLC patients with the EGFR-T790M mutation.

scholarly journals Mechanisms of Resistance to EGFR TKIs and Development of a New Generation of Drugs in Non-Small-Cell Lung Cancer

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Takayuki Kosaka ◽  
Ei Yamaki ◽  
Akira Mogi ◽  
Hiroyuki Kuwano
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
Clinical Problem ◽  
Small Cell ◽  
Small Cell Lung ◽  
Egfr Tkis

Gefitinib and erlotinib, which are epidermal growth factor receptor- (EGFR-) specific tyrosine kinase inhibitors (TKIs), are widely used as molecularly targeted drugs for non-small-cell lung cancer (NSCLC). Currently, the search forEGFRgene mutations is becoming essential for the treatment of NSCLC since these have been identified as predictive factors for drug sensitivity. On the other hand, in almost all patients responsive to EGFR-TKIs, acquired resistance is a major clinical problem. Mechanisms of acquired resistance reported in the past few years include secondary mutation of theEGFRgene, amplification of theMETgene, and overexpression of HGF; novel pharmaceutical agents are currently being developed to overcome resistance. This review focuses on these mechanisms of acquired resistance to EGFR-TKIs and discusses how they can be overcome.

Response to Osimertinib in a Patient With Non-Small Cell Lung Cancer and Two Uncommon EGFR mutations

2020 ◽  
pp. 10-13
Author(s):  
Christoforos Astaras ◽  
Adrienne Bettini ◽  
Daniel C. Betticher
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Genetic Alterations ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Exon 20

In advanced non-small cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) mutations are one of the most frequent oncogenic drivers. They confer a favorable prognosis and strongly predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Over the last decades, several EGFR genetic alterations, common and uncommon mutations, have been described in exons 18−21. Common mutations are exon 19 deletions (most frequently E746-A750) and exon 21 L858R substitution. Uncommon mutations include exon 18 G719X, exon 20 S768l, exon 21 L861Q and many other rare ones. This report describes the case of a 55-year-old woman with a newly diagnosed metastatic lung adenocarcinoma harboring two rare EGFR mutations and showing sustained response to osimertinib.

scholarly journals Severe gastrointestinal bleeding due to erlotinib and celecoxib therapy: additional effect?

2016 ◽  
Vol 10 ◽  
Author(s):  
Maddalena Zippi ◽  
Angeloluca De Quarto ◽  
Chiara Marzano ◽  
Claudio Cassieri ◽  
Pietro Crispino ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Prior History ◽  
Small Cell Lung ◽  
Increased Risk ◽  
Egfr Tkis

Non-small cell lung cancer (NSCLC) is the leading cause of cancer related dead worldwide and account for over 85% of all lung cancers. Furthermore, the majority of patients with NSCLC present with advanced, metastatic disease at the time of diagnosis. For most patients with non-small cell lung cancer, current treatments do not cure the cancer. Therefore, there is a great need for development of more effective therapies. The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) like erlotinib and gefitinib have been recognized as an important molecular target in cancer therapy and they are approved for the treatment of refractory advanced NSCLC patients. EGFR TKIs are generally well tolerated. The two most common toxicities include dermatologic and gastrointestinal side effects. Cases of gastrointestinal perforation, some of which were fatal, have also been reported in patients receiving erlotinib. Those at increased risk include those taking concomitant anti-angiogenic agents, corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and/or taxane-based chemotherapy, or who have prior history of peptic ulceration or diverticular disease.

scholarly journals Predictive molecular markers for EGFR-TKI in non-small cell lung cancer patients: new insights and critical aspects

2010 ◽  
Vol 1 (1) ◽  
pp. 10 ◽  
Author(s):  
Paola Ulivi ◽  
Daniele Calistri ◽  
Wainer Zoli ◽  
Dino Amadori
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Objective Response ◽  
Small Cell ◽  
Correct Selection ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Egfr Tkis

In recent years, a number of novel agents have been investigated that target specific molecular pathways in non-small cell lung cancer (NSCLC). A great deal of effort has been focused on identifying specific markers that predict treatment response, given that a tailored approach would maximize both the therapeutic index and the cost-effectiveness. The epidermal growth factor receptor (EGFR) pathway has emerged as a key regulator of cancer cell proliferation and invasion, and several specific EGFR inhibitors have been examined. Gefitinib and erlotinib are selective EGFR tyrosine kinase inhibitors (EGFR-TKIs), demonstrating good results in selected cases both in terms of objective response rate and of overall survival. At present, EGFR gene mutations are the best positive predictive factors for TKI therapy, and a number of other potential biomarkers are being investigated as additional positive or negative predictors of response. The correct selection of patients that could benefit from these innovative therapies, based on an accurate molecular characterization, is mandatory to provide the best clinical management. Currently, the main factor limiting the characterization of metastatic NSCLC patients is the small quantity of tumor cells available for molecular analysis. In this paper we provide an overview of the most important molecular predictive markers for EGFR-TKIs therapy in NSCLC patients, and focus attention on biological samples suitable for analysis and alternative sampling approaches such as plasma- or serum-derived DNA.

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