Diaphragmatic hernia during treatment of lung cancer harboring an EGFR mutation

ABSTRACT Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a first-line treatment for patients with nonsmall-cell lung cancer harboring EGFR mutations. We report a 65-year-old Japanese woman with nonsmall-cell lung cancer taking an EGFR-TKI who visited the emergency department with acute nausea and vomiting. Imaging studies demonstrated an incarcerated diaphragmatic hernia. Urgent diagnostic surgery revealed a gap in the diaphragm acting as a hernial orifice, where a metastatic tumor was detected. We consider that regression of the diaphragmatic metastasis by EGFR-TKI therapy resulted in perforation of the diaphragm, causing the diaphragmatic hernia. Gastrointestinal adverse events, e.g. nausea, vomiting and diarrhea, are common during EGFR-TKI treatment. However, this case suggests that in patients with diaphragmatic metastasis, we should consider the rare possibility of diaphragmatic perforation and a subsequent hernia.

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

healthbook TIMES Oncology Hematology ◽

10.36000/hbt.oh.2020.03.011 ◽

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.

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Nonsmall Cell Lung Cancer Therapy: Insight into Multitargeted Small-Molecule Growth Factor Receptor Inhibitors

BioMed Research International ◽

10.1155/2013/964743 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 10

Author(s):

Mridul Roy ◽

Yu-Hao Luo ◽

Mao Ye ◽

Jing Liu

Keyword(s):

Lung Cancer ◽

Growth Factor ◽

Cell Lung Cancer ◽

Kinase Inhibitors ◽

Single Agent ◽

Growth Factor Receptor ◽

Cancer Therapeutics ◽

Nonsmall Cell Lung Cancer ◽

Combination Strategies ◽

Self Sufficiency

To date, lung cancer is the leading cause of cancer-related death worldwide, among which nonsmall cell lung cancer (NSCLC) comprises about 85%. Taking into account the side effects of surgery, radiation, platinum-based doublet chemotherapy, and the growth self-sufficiency characteristic of cancer cells, drugs have been discovered toward growth factor receptor (GFR) to treat NSCLC. As expected, these drugs provide a greater benefit. To increase the efficacy of such growth factor receptor tyrosine kinase inhibitors (RTKIs), coinhibition of GFR signaling pathways and combination of inhibitors along with radiation or chemotherapy have drew intense insight. Although clinical trials about single-agent RTKIs or their combination strategies suggest their increase potency against cancer, they are not beyond adverse effects, and sometimes the effects are more deadly than chemotherapy. Nevertheless the hope for RTKIs may be proved true by further researches and digging deep into cancer therapeutics.

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Modern vector in treatment of patients with lung cancer: tyrosine kinase inhibitors in epidermal growth factor receptor mutations (literature review)

Medicni perspektivi (Medical perspectives) ◽

10.26641/2307-0404.2021.2.234379 ◽

2021 ◽

Vol 26 (2) ◽

pp. 4-11

Author(s):

O.M. Smorodska ◽

Yu.V. Moskalenko ◽

I.O. Vynnychenko ◽

O.I. Vynnychenko ◽

V.V. Kostuchenko

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Kinase Inhibitors ◽

Acquired Resistance ◽

Growth Factor Receptor ◽

Small Cell ◽

Small Cell Lung ◽

Epidermal Growth ◽

Egfr Tki

Tumor molecular profiling in patients with non-small cell lung cancer (NSCLC) is used to identify driver mutations, which lead to premature carcinogenesis in more than 80% of adenocarcinoma cases, including epidermal growth factor receptor (EGFR) mutations. Identification of specific somatic aberrations allows to personalize treatment. Personalization of treatment resulted in improvement of NSCLC outcomes. The aim of our study was to consider scientific data on modern concepts of treatment of patients with non-small cell lung cancer with previously detected oncogenic mutations, especially EGFR mutation. In our study we analyzed scientific papers and data of international scientific literature on the problem of lung cancer treatment. Methods used: scientific research, analytical and generalizing. Different drugs are used in treatment of lung cancer. Choice of treatment scheme depends on type and presence of mutations. Patients with advanced non-small-cell lung cancer and detected mutation in the EGFR can be treated with tyrosine kinase inhibitors (TKIs). Nowadays three first generation drugs are recommended by FDA: afatinib, erlotinib, gefitinib. They showed good clinical benefit. Most patients with metastatic NSCLC typically show disease progression after approximately 9 to 13 months of erlotinib, gefitinib, or afatinib therapy. The first and only commercially available third-generation EGFR TKI is оsimertinib - an oral drug, which selectively inhibits both EGFR-TKI and EGFR T790M resistance mutations. Nowadays scientists are in active investigation of mechanisms of acquired resistance to TKIs, but little is known yet. Clinical success can be observed in patients who were treated with TKIs. EGFR T790M is a mutation that leads to acquired resistance to EGFR TKI therapy. Its incidence is approximately 60% after disease progression on TKI drugs (erlotinib, gefitinib, or aphatinib). Third-generation EGFR TKIs demonstrate high efficacy, but acquired resistance development cannot be avoided. Mechanisms of acquired resistance to these agents are still investigated.

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

Current Oncology ◽

10.3390/curroncol29010024 ◽

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.

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

10.21203/rs.3.rs-697509/v1 ◽

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.

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The Frequency of Epidermal Growth Factor Receptor Mutation of Nonsmall Cell Lung Cancer according to the Underlying Pulmonary Diseases

Pulmonary Medicine ◽

10.1155/2011/290132 ◽

2011 ◽

Vol 2011 ◽

pp. 1-5 ◽

Cited By ~ 13

Author(s):

Kazuhiro Usui ◽

Tomonori Ushijima ◽

Yoshiaki Tanaka ◽

Chiharu Tanai ◽

Hiromichi Noda ◽

...

Keyword(s):

Lung Cancer ◽

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Cell Lung Cancer ◽

Egfr Mutation ◽

Growth Factor Receptor ◽

Nonsmall Cell Lung Cancer ◽

Epidermal Growth ◽

Egfr Tki

Background. Although epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are effective in patients with nonsmall cell lung cancer with epidermal growth factor receptor (EGFR) mutation, EGFR-TKIs have a risk of inducing fatal interstitial lung disease (ILD). The selection of chemotherapy based on the EGFR mutation status is recommended, however, the frequency of EGFR mutation in patients with ILD and the efficacy and safety of EGFR-TKI in patients with ILD and EGFR mutation are unknown.Methods. We retrospectively reviewed the association of the EGFR mutation status of nonsmall cell lung cancer and pulmonary diseases. Based on high-resolution computed tomography (HRCT) performed at diagnosis of lung cancer, patients were categorized into three groups: normal, emphysema, and fibrosis.Results. Of 198 patients with nonsmall cell lung cancer, we identified 52 (26.3%) patients with an EGFR mutation. EGFR mutations were identified in 43 (35.2%) of 122 patients with normal lungs, 8 (13.6%) of 59 with emphysema, and 1 (5.9%) of 17 with pulmonary fibrosis. Of the 52 patients with EGFR mutation, 43 patients received gefitinib. One patient with an EGFR mutation and fibrosis developed fatal ILD. There was not a significant difference in median overall survival from gefitinib treatment between never-smokers and smokers (797 days versus not reached; ).Conclusions. Patients with sensitive EGFR mutation and normal lungs may benefit from an EGFR-TKI treatment even if they have smoking history.

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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

Case Reports in Oncology ◽

10.1159/000513904 ◽

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.

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A Case Report of Primary Resistance to EGFR TKI in Lung Adenocarcinoma Due to Coexisting MET Exon 14 Skipping Mutation with Excellent Response to Combination of Gefitinib and Capmatinib

Indian Journal of Medical and Paediatric Oncology ◽

10.1055/s-0041-1731851 ◽

2021 ◽

Author(s):

Nirmal Vivek Raut ◽

Siddharth Srivastava ◽

Guarav Dilip Gangwani ◽

Heena Sajid Ali

Keyword(s):

Kinase Inhibitors ◽

Single Gene ◽

Growth Factor Receptor ◽

Nonsmall Cell Lung Cancer ◽

Primary Resistance ◽

Gene Testing ◽

Comprehensive Genomic Profiling ◽

Egfr Tyrosine Kinase Inhibitors ◽

Next Generation Sequencing Ngs ◽

Egfr Tki

AbstractTreatment of nonsmall cell lung cancer (NSCLC) carrying an epidermal growth factor receptor (EGFR) mutation depends on EGFR tyrosine kinase inhibitors (TKIs). However, all patients treated with EGFR TKI eventually develop progressive disease. Approximately, 20% of patients do not respond to EGFR TKIs, which is defined as primary resistance. The prognosis of these patients is similar to NSCLC with nondriver mutations. We report a case of a patient with EGFR exon 21 mutation who rapidly progressed in 15 days on Gefitinib. Next-generation sequencing (NGS) showed a MET exon 14 skip mutation coexisting with EGFR exon 21 mutation, causing primary resistance to EGFR TKI. Based on NGS reports, a treatment combining Gefitinib and Capmatinib, a MET inhibitor, induced a rapid response in the patient, which was sustained at the end of 8 months. This clearly emphasizes the need for comprehensive genomic profiling using NGS over single gene testing.

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