scholarly journals Uncommon EGFR Compound Mutations in Non-Small Cell Lung Cancer (NSCLC): A Systematic Review of Available Evidence

2022 ◽  
Vol 29 (1) ◽  
pp. 255-266
Author(s):  
Ilaria Attili ◽  
Antonio Passaro ◽  
Pasquale Pisapia ◽  
Umberto Malapelle ◽  
Filippo de Marinis
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
First Generation ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung

Compound epidermal growth factor receptor (EGFR) mutations represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) patients with uncommon EGFR mutations. We conducted a systematic review to investigate the available data on this patients’ subgroup. Overall, we found a high heterogeneity in the incidence of compound mutations (4–26% of total EGFR mutant cases), which is dependent on the different testing methods adopted and the specific mutations considered. In addition, the relative incidence of distinct compound subclasses identified is reported with extreme variability in different studies. Preclinical and clinical data, excluding de novoEGFR exon 20 p.T790M compound mutations, show good responses with EGFR tyrosine kinase inhibitors (TKIs) (combined common mutations: response rate (RR) ≥ 75% with either first- or second-generation TKIs; combined common plus uncommon: RR 40–80% and 100% with first-generation TKIs and afatinib, respectively; combined uncommon: RR 20–70%, ~80% and ~75% with first-generation TKIs, afatinib and osimertinib, respectively). Overall, data are consistent in supporting the use of EGFR TKIs in treating compound EGFR mutations, taking into account different sensitivity profile of accompanying EGFR mutations for selecting the most adequate EGFR TKI for individual patients.

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 Real-world Outcomes of First-line Afatinib in Patients with Non-small Cell Lung Cancer and Uncommon EGFR Mutations in South Korea

2021 ◽  
Author(s):  
Mi-Hyun Kim ◽  
Chang Min Choi ◽  
Sung Yong Lee ◽  
Cheol Kyu Park ◽  
Yoon Soo Chang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
De Novo ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Exon 20

Abstract Uncommon epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) are heterogeneous and show variable prevalence and clinical responses to EGFR-tyrosine kinase inhibitors. We investigated the characteristics of uncommon EGFR mutations and the clinical efficacy of afatinib in patients. In this multicenter, retrospective study, we analyzed patients with NSCLC and uncommon EGFR mutations; these were categorized according to their incidence: (1) major uncommon mutations (G719X and L861Q), (2) compound mutations, and (3) minor uncommon mutations (exon 20 insertion, S768I, and de novo T790M). Sixty-four patients (9.1%, 64/703) with uncommon EGFR mutations were identified in 16 South Korean institutes. Afatinib demonstrated activity against major uncommon (median time of treatment [TOT]: 20.3 months, 95% CI: 5.0-27.9; overall survival (OS): 30.6 months, 95% CI: 33.5–34.0) and compound mutations (median TOT: 11.9 months, 95% CI: 3.6–9.6; OS: 29.1 months, 95% CI: 12.1–65.4). Minor uncommon mutations showed unfavorable responses to afatinib (median TOT: 3.8 months, 95% CI: 2.1–4.2; OS: 8.5 months, 95% CI: 4.7–18.2). S768I mutation was present in 14 patients (1.99%, 14/703). Median TOT and OS were not significantly different between S768I and resistant exon 20 mutations. Afatinib is active in patients with NSCLC harboring major uncommon and compound EGFR mutations.

scholarly journals Combination of Crizotinib and Osimertinib in T790M+ EGFR-Mutant Non-Small Cell Lung Cancer with Emerging MET Amplification Post-Osimertinib Progression in a 10-Year Survivor: A Case Report

2021 ◽  
pp. 477-482
Author(s):  
Miriam Blasi ◽  
Daniel Kazdal ◽  
Michael Thomas ◽  
Petros Christopoulos ◽  
Mark Kriegsmann ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Met Amplification ◽  
Egfr Mutant

Tyrosine kinase inhibitors (TKIs) represent the standard treatment for patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. The duration of the response is, however, limited in time owing to the development of resistance mechanisms to both first- and second-generation agents such as MET oncogene amplification. This report describes the successful results obtained with the combination of the third-generation TKI osimertinib with the multitargeted TKI and MET inhibitor crizotinib in a patient with EGFR-mutant NSCLC with emerging MET amplification with a tolerable toxicity profile.

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 Network meta-analyses for EGFR mutation-positive non-small-cell lung cancer: systematic review and overview of methods and shortcomings

2020 ◽  
Vol 9 (17) ◽  
pp. 1179-1194
Author(s):  
Carl Samuelsen ◽  
Ingolf Griebsch
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Small Cell ◽  
Future Research ◽  
Small Cell Lung ◽  
Meta Analyses

Aim: To perform a review of network meta-analyses (NMAs) for the first-line treatment of EGFR mutation-positive non-small-cell lung cancer, and to provide an overview of methodological approaches and potential shortcomings. Materials & methods: We conducted a systematic review of NMAs and evaluated their methodologies, including inclusion/exclusion criteria, information sources, results and outcomes, and statistical methodologies. Results: We identified ten published NMAs using five archetypical network structures. Despite similar objectives, there was substantial variability in the number of trials included in each NMA and in the relative treatment efficacy of the tyrosine kinase inhibitors. Conclusion: We identified methodological issues to explain differences in the findings, criteria for inclusion in NMAs and the degree of lumping of treatments. These factors should be given particular consideration in future research.

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.

scholarly journals ASCO 2021—selection of personal highlights in early stage non-small cell lung cancer

2021 ◽  
Author(s):  
Gudrun Absenger ◽  
Andreas Pircher
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Early Stage ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Adjuvant Setting ◽  
Small Cell Lung ◽  
Early Stage Nsclc

SummaryThis article intends to summarize personal non-small cell lung cancer (NSCLC) highlights of the virtual ASCO 2021 meeting. Immunotherapy is now a mainstay of advanced stage NSCLC treatment and there are several ongoing studies investigating the role of immunotherapy in early stage NSCLC. At ASCO 2021 the first data on atezolizumab in the adjuvant setting were presented and give a positive signal that immunotherapy will also become an option for patient in early stage NSCLC. Furthermore, overall survival (OS) updates of two studies investigating the effects of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the adjuvant setting of EGFR-mutated NSCLC patients were presented. In conclusion ASCO 2021 provided the lung cancer community with inspiring new data especial in early stages and challenges the community with integration of these data into our daily clinical routine.

scholarly journals Continued gefitinib retreatment beyond progression in patients with advanced non-small cell lung cancer harboring sensitive EGFR mutations

2020 ◽  
Vol 48 (10) ◽  
pp. 030006052095503
Author(s):  
Xuhong Jiang ◽  
Xiaoqing Li ◽  
Lingli Tu ◽  
Jin Cai ◽  
Man Wei ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Disease Progression ◽  
Cell Lung Cancer ◽  
Evaluation Criteria ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung

Purpose To evaluate the effectiveness and safety of gefitinib retreatment beyond disease progression in patients with advanced non-small cell lung cancer (NSCLC) with sensitive epidermal growth factor receptor ( EGFR) mutations. Methods Data from patients with stage III/IV NSCLC were analyzed retrospectively. Patients with sensitive EGFR mutations received first-line treatment with gefitinib followed by retreatment with gefitinib after disease progression. Progression-free survival (PFS) after the first treatment (PFS-1) was defined as the time to progression or death using the Response Evaluation Criteria in Solid Tumors criteria (RECIST) v1.1 criteria. The second PFS (PFS-2) was defined as the interval between the first and second progressions, at the investigator’s discretion. Toxicities were recorded in accordance with the National Cancer Institute (NCI)-Common Terminology Criteria (CTC) version 4.0. Results Sixteen patients aged 53 to 80 years (median 66 years) were included in the analysis. The median PFS-1 and PFS-2 were 10.0 months and 14.0 months, respectively. The median overall survival (OS) was 36.0 months. No toxicity of grade 3 or worse was observed. Conclusions Our findings suggest that gefitinib retreatment beyond disease progression may be an effective and tolerable approach for NSCLC patients with sensitive EGFR mutations.

Role of Cytomorphology in the Era of Liquid Biopsy

2019 ◽  
Vol 63 (6) ◽  
pp. 497-505 ◽  
Author(s):  
Eduardo Clery ◽  
Pasquale Pisapia ◽  
Elena Vigliar ◽  
Umberto Malapelle ◽  
Claudio Bellevicine ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Morphological Changes ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
Large Cell ◽  
Small Cell ◽  
Small Cell Lung

In the late stages of non-small cell lung cancer, the detection of sensitizing mutations of the epidermal growth factor receptor (EGFR) is mandatory to select patients’ treatment with first- or second-generation tyrosine kinase inhibitors (TKIs). In patients showing progressive disease, the assessment of the EGFR exon 20 resistance point mutation p.T790M is required for third-generation TKI administration. However, molecular analysis does not capture all the different mechanisms of resistance against these molecules. A variety of morphological changes associated with acquired resistance have also been described. Since an altered morphology may be the only clue to acquired resistance, cytopathology still plays a relevant role in this setting. In this comprehensive review, we have focused on the relevance of squamous cell carcinoma, small cell lung cancer and large-cell neuroendocrine carcinoma transitions from adenocarcinoma resistant to TKIs.

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