scholarly journals Coexistence of ALK rearrangement in lung adenocarcinoma harbouring EGFR mutation: Real-World Data From a Single-Institution Experience

2021 ◽  
Author(s):  
Wei-Xiang Zhong ◽  
Xi-Feng Wei
Keyword(s):  
Targeted Therapy ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Clinicopathological Features ◽  
Alk Rearrangement ◽  
First Choice ◽  
Positive Rate ◽  
Epidermal Growth ◽  
Egfr Tkis

Abstract Background Concomitance of epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement have been increasingly reported in lung adenocarcinoma (LUAD). However, the biological mechanism, clinicopathological features and optimization of targeted drugs remain unclear. This study aimed to explore the clinicopathological characteristics of coexisting mutations of EGFR and ALK genes in LUAD patients, with hopes of scientifically guiding such patients towards selected, targeted drugs. Methods Two hundred and thirty-seven cases of LUAD were enrolled. Mutations in exons 18, 19, 20 and 21 of the EGFR gene were detected by the amplification refractory mutation system-peptide nucleic acid (ARMS-PNA) technique, while expression of the ALK fusion gene was detected by the 5′/3′ imbalance strategy for reverse transcription, followed by quantitative polymerase chain reaction (RT–qPCR) analysis. The clinicopathological features of patients with coexisting mutations of EGFR and ALK genes were analysed retrospectively, and the follow-up data of these patients were collected. Results There were 6 cases with coexisting mutations of EGFR and ALK genes, which were more common in women, non-smoking and stage IV LUAD with bone metastasis, hence a positive rate of 2.53% (6/237). Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were the first choice for targeted therapy in patients with LUAD harbouring coexisting mutations of EGFR and ALK genes in Gannan region, and the progression-free survival (PFS) was between 2-6 months. Conclusions These results indicated that the positive rate of coexisting mutations of EGFR and ALK genes in LUAD patients in the Gannan region was relatively high; these genes were more common in women, non-smokers and stage IV patients with bone metastasis. EGFR-TKIs were the first choice for targeted therapy in these patients, but the therapeutic effect was limited. EGFR-TKI combined with ALK-TKI dual targeted therapy may be a more effective treatment.

Two different patterns of lung adenocarcinoma with concomitant EGFR mutation and ALK rearrangement

2021 ◽  
pp. 030089162110055
Author(s):  
Dashi Zhao ◽  
Jun Fan ◽  
Li Peng ◽  
Bo Huang ◽  
Yili Zhu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Alk Rearrangement ◽  
Molecular Alterations ◽  
Anaplastic Lymphoma ◽  
Sporadic Cases ◽  
Epidermal Growth ◽  
Rare Group

Epidermal growth factor receptor ( EGFR) mutations and anaplastic lymphoma kinase ( ALK) rearrangements are considered mutually exclusive in non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma (LUAC). However, sporadic cases harboring concomitant EGFR and ALK alterations have been increasingly reported. There is no consensus opinion regarding the treatment of patients positive for both molecular alterations. NSCLC with EGFR/ ALK coalterations should be separated into two subtypes: unifocal and multifocal LUAC. Here, we present an overview of the available literature regarding this rare group of patients to provide useful suggestions for therapeutic strategies.

scholarly journals The Journey of an EGFR-Mutant Lung Adenocarcinoma through Erlotinib, Osimertinib and ABCP Immunotherapy Regimens: Sensitivity and Resistance

2019 ◽  
Vol 12 (3) ◽  
pp. 765-776 ◽  
Author(s):  
Albina Kibirova ◽  
Malcolm D. Mattes ◽  
Matthew Smolkin ◽  
Patrick C. Ma
Keyword(s):  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Tumor Response ◽  
Checkpoint Inhibitors ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
Epidermal Growth ◽  
Egfr Mutant ◽  
Egfr Tkis ◽  
Guided Therapy

Patients with epidermal growth factor receptor (EGFR) mutation positive non-small cell lung cancer (NSCLC) have several EGFR targeting tyrosine kinase inhibitors (TKIs) available in frontline management. However, the disease will inevitably progress over time due to acquired resistance. Longitudinal tumor profiling for genomics guided therapy is indicated upon disease progression. It is a common scenario yet, when after failure of EGFR-TKIs, potentially actionable genomic alterations are lacking. Management of such patient is challenging with very limited options available. Combination of chemotherapy, anti-vascular/anti-angiogenic and immune-checkpoint inhibitors may become a salvage option for such patients. Here we describe a case of TKI refractory EGFR-mutant NSCLC successfully treated with carboplatin, paclitaxel, atezolizumab and bevacizumab combination with remarkable prompt tumor response.

scholarly journals Tumour Content Ratio Matters for Detecting Epidermal Growth Factor Receptor Mutation by Cobas Test in Small Biopsies; a Retrospective Study

2019 ◽  
Author(s):  
Mariko Kogo ◽  
Daichi Fujimoto ◽  
Kazutaka Hosoya ◽  
Kazuma Nagata ◽  
Atsushi Nakagawa ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Egfr Mutation ◽  
False Negative ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Content Ratio ◽  
Positive Rate ◽  
Epidermal Growth ◽  
Tumour Cellularity ◽  
Egfr Mutated

Abstract Background Recent studies indicate the benefit of treatment with osimertinib over that with conventional epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) for untreated EGFR -mutated non-small cell lung cancer (NSCLC). Cobas ver2 is the only companion diagnostic method for detecting EGFR mutations with osimertinib treatment. We clinically experience false negative cases with this test, but its actual sensitivity is unknown. Moreover, no study has suggested the importance of tumour dissection, and most facilities do not routinely perform them on small biopsies. The purpose of this study was to evaluate the sensitivity of cobas in clinical practice and clarify the role of dissection as a component of the cobas testing Materials and Methods We examined 132 patients with EGFR -mutated NSCLC diagnosed by bronchoscopy and confirmed with PCR clamp. Patients were tested with cobas and the EGFR -positive rate was calculated. Samples with undetected EGFR mutations were retested after tumour dissection and the rate of samples whose EGFR mutation was corrected to positive was assessed. To evaluate tumour cellularity, the tumour content ratio was assessed by calculating tumour cell count over the total cell count on the slide. Results The positive rate of EGFR mutation identification was 76% with cobas, although EGFR mutation-negative patients retained responses to TKI therapy equivalent to positive patients did; however, the tumour content ratio of negative samples was significantly lower than that of positive samples. Twenty-nine negative samples underwent dissection and 24% were corrected to positive. Moreover, 53% of the samples with a tumour content ratio below 10% was negative for cobas, but 33% of these turned positive after dissection. Conclusion Cobas had a high false negative rate in clinical practice, and tumour content ratio might be associated with this rate. Dissection could improve the sensitivity of cobas, especially in samples with low tumour cellularity.

Reflex Testing for Epidermal Growth Factor Receptor Mutation and Anaplastic Lymphoma Kinase Fluorescence In Situ Hybridization in Non–Small Cell Lung Cancer

2011 ◽  
Vol 135 (5) ◽  
pp. 655-664
Author(s):  
Mari Mino-Kenudson ◽  
Eugene J. Mark
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Molecular Testing ◽  
Small Cell Lung ◽  
Alk Rearrangement ◽  
Anaplastic Lymphoma ◽  
Epidermal Growth

Abstract Context.—Non–small cell lung cancer (NSCLC) is a poor-prognosis malignancy for which more effective treatments are needed, with accumulating clinical experiences supporting benefits of receptor tyrosine kinase inhibitors for patients with tumors harboring an epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement. Objective.—To review completed and ongoing clinical trials of EGFR tyrosine kinase inhibitors for EGFR mutation–positive NSCLC and an ALK inhibitor for those with ALK rearrangement, while also exploring practical issues surrounding the implementation of molecular testing as a routine component of the diagnostic workup of NSCLC in the United States. Data Sources.—Published biomedical literature, abstracts presented at recent major oncology meetings, and ClinicalTrials.gov. Conclusions.—Continually evolving evidence indicates the possible efficacy of molecularly targeted agents for the treatment of advanced NSCLC, especially adenocarcinoma. To identify patients who will most likely benefit from the targeted therapy, routine determination of the corresponding genetic alterations after histologic diagnosis of NSCLC (reflex molecular testing for EGFR mutations and ALK rearrangement) should be considered.

scholarly journals Treatment choice in epidermal growth factor receptor mutation-positive non-small cell lung carcinoma: latest evidence and clinical implications

2017 ◽  
Vol 9 (3) ◽  
pp. 201-216 ◽  
Author(s):  
Oscar Juan ◽  
Sanjay Popat
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Egfr Mutation ◽  
Small Cell Lung Carcinoma ◽  
Growth Factor Receptor ◽  
Subsequent Development ◽  
Cell Lung Carcinoma ◽  
Epidermal Growth ◽  
Egfr Tkis

Discovery of sensitizing mutations in epidermal growth factor receptor ( EGFR) and the subsequent development of EGFR tyrosine kinase inhibitors (TKIs) have substantially changed the treatment of lung cancer. First-line treatment with EGFR TKIs (gefitinib, erlotinib and afatinib) has demonstrated a superior response rate and progression-free survival (PFS) compared with chemotherapy in EGFR-mutation positive patients. However, a number of open questions remain, such as choice between the three EGFR TKIs licensed, treatment of patients unsuitable for chemotherapy due to morbidity or advanced age, management of acquired resistance and optimal biological sample to determine EGFR status. Recently the first head-to-head trial comparing gefitinib and afatinib (LUX-Lung 7) has been reported. Moreover, third-generation EGFR TKIs such as osimertinib, rociletinib, olmutinib and ASP8273, with preferential activity against T790M mutant tumours, the commonest resistance mechanism to EGFR TKIs, have shown promising results in early clinical trials, with osimertinib now licensed. In this review, we summarize latest advances in the treatment of EGFR-mutation positive patients focusing on controversial areas and emerging challenges to optimally treat these patients in the future.

Clinicopathological features in correlation with epidermal growth factor receptor gene mutations in non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21148-21148 ◽  
Author(s):  
F. Tanaka ◽  
S. Matsumoto ◽  
T. Takuwa ◽  
N. Kondo ◽  
Y. Okumura ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Fdg Uptake ◽  
Epidermal Growth ◽  
The Mean ◽  
Egfr Mutated ◽  
Egfr Tkis

21148 Background: Mutations in the epidermal growth factor receptor (EGFR) gene are found in 10–30% of non-small cell lung cancer, and are useful to predict the efficacy of EGFR-tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib and erlotinib. However, it is sometimes difficult to examine such mutations. Thus, prediction of presence or absence of EGFR mutations, correlated with clinical response to EGFR-TKIs, based on clinicopathological characteristics may be important in clinical practice. Methods: We retrospectively assessed EGFR-mutation status in correlation with clinical features including FDG-PET findings and pathological features including presence or absence of bronchioalveolar component (BAC) in adenocarcinoma (Ad) case. A total of 72 consecutive patients (24 females; mean age, 65 years; 40 Ad cases) who received thoracotomy from August 2005 through October 2006 were reviewed Results: Sixteen cases (22%) had EGFR-mutations (8 cases each in exon 19 and exon 21). The incidence of EGFR-mutation was significantly higher in female (42%) or never-smoker (60%) than in male (13%) or smoker (15%). EGFR-mutation was almost exclusively found in Ad; among Ad cases, there was no significant difference in the incidence of EGFR-mutation between BAC-positive (47%) and BAC-negative cases (29%; p=0.33). Among 61 cases who received FDG-PET scan prior to thoracotomy, only 15% of EGFR- mutated cases had higher FDG-uptake, whereas 47% of EGFR-wild cases had higher FDG-uptake (p=0.36); the sensitivity and specificity of lower FDG-uptake to predict the presence of EGFR-mutations were 71% and 53%, respectively. The positive predictive value (PPV) of lower- FDG-uptake for the presence of EGFR-mutations was only 29%, but the negative predictive value (NPV) was as high as 85%. The mean standardized uptake value (SUV) of FDG for EGFR-wild patients and EGFR-mutated patients were 5.7 and 3.3, respectively (p=0.11). The mean SUV for tumors mutated in exon 19 seemed to be lower than that for tumors mutated in exon 21 (1.8 versus4.6). Conclusions: Higher FDG-uptake combined with clinical features (male and smoker) may help to exclude patients with EGFR-wild tumors who may not respond to EGFR-TKIs treatment. No significant financial relationships to disclose.

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