EP1.01-59 The Effectiveness of Osimertinib in a NSCLC Patient with Complex Uncommon EGFR Mutations of G719X and S768I: A Case Report

Introduction Most patients with non-small-cell lung cancer tumors that have epidermal growth factor receptor (EGFR) mutations have deletion mutations in exon 19 or exon 21, or both.In recent years, targeted therapies in lung cancer have increased survival, but the development of resistance to these drugs poses a major problem. Thesubstitution of methionineforthreonine at position 790 (T790M) mutation,is primarily responsible for this resistance. However, after osimertinib used in T790M positivepatients treatment options are generally limited to chemotherapy. Case report We reported the efficacy of erlotinib, which we reapplied due to the disappearance of the resistance mutation after osimertinib in a 68-year-old patient using osimertinib after erlotinib. Management and outcome: In the patient using erlotinib due to exon 19 deletion when progression was observed and T790M positivity was detected, osimertinib treatment was initiated. However, when T790M was found to be negative with rebiopsy in progression after osimertinib, a complete response was achieved by restarting erlotinib. Discussion The strategy of restarting erlotinib treatment with negative T790M mutation detected in biopsies of patients with osimertinib resistance may be an acceptable treatment option.

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Peptide-Affinity Precipitation of Extracellular Vesicles and Cell-Free DNA Improves Sequencing Performance for the Detection of Pathogenic Mutations in Lung Cancer Patient Plasma

International Journal of Molecular Sciences ◽

10.3390/ijms21239083 ◽

2020 ◽

Vol 21 (23) ◽

pp. 9083

Author(s):

Catherine Taylor ◽

Simi Chacko ◽

Michelle Davey ◽

Jacynthe Lacroix ◽

Alexander MacPherson ◽

...

Keyword(s):

Lung Cancer ◽

Extracellular Vesicles ◽

Liquid Biopsy ◽

Nsclc Patient ◽

Egfr Mutations ◽

Single Nucleotide Variants ◽

Cell Free Dna ◽

Free Dna ◽

Nsclc Patients ◽

Peptide Affinity

Liquid biopsy is a minimally-invasive diagnostic method that may improve access to molecular profiling for non-small cell lung cancer (NSCLC) patients. Although cell-free DNA (cf-DNA) isolation from plasma is the standard liquid biopsy method for detecting DNA mutations in cancer patients, the sensitivity can be highly variable. Vn96 is a peptide with an affinity for both extracellular vesicles (EVs) and circulating cf-DNA. In this study, we evaluated whether peptide-affinity (PA) precipitation of EVs and cf-DNA from NSCLC patient plasma improves the sensitivity of single nucleotide variants (SNVs) detection and compared observed SNVs with those reported in the matched tissue biopsy. NSCLC patient plasma was subjected to either PA precipitation or cell-free methods and total nucleic acid (TNA) was extracted; SNVs were then detected by next-generation sequencing (NGS). PA led to increased recovery of DNA as well as an improvement in NGS sequencing parameters when compared to cf-TNA. Reduced concordance with tissue was observed in PA-TNA (62%) compared to cf-TNA (81%), mainly due to identification of SNVs in PA-TNA that were not observed in tissue. EGFR mutations were detected in PA-TNA with 83% sensitivity and 100% specificity. In conclusion, PA-TNA may improve the detection limits of low-abundance alleles using NGS.

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T790M mutation in stage IV EGFR-mutated NSCLC patient with acquired resistance reverted to original 19Del mutation after administration of a series of precision treatments: a case report

Precision Clinical Medicine ◽

10.1093/pcmedi/pby013 ◽

2018 ◽

Vol 1 (3) ◽

pp. 129-133 ◽

Cited By ~ 1

Author(s):

Jialong Han ◽

Ya Wang ◽

Lili Zhong ◽

Huijie Zhou ◽

Min Yu ◽

...

Keyword(s):

Case Report ◽

Nsclc Patient ◽

Acquired Resistance ◽

Stage Iv ◽

T790m Mutation ◽

Egfr Mutated

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EGFR-tyrosine kinase inhibitor treatment in a patient with advanced non-small cell lung cancer and concurrent exon 19 and 21 EGFR mutations: A case report and review of the literature

Oncology Letters ◽

10.3892/ol.2016.4409 ◽

2016 ◽

Vol 11 (5) ◽

pp. 3546-3550 ◽

Cited By ~ 10

Author(s):

YANG YANG ◽

BIAO ZHANG ◽

RUTIAN LI ◽

BAORUI LIU ◽

LIFENG WANG

Keyword(s):

Lung Cancer ◽

Case Report ◽

Kinase Inhibitor ◽

Small Cell ◽

Egfr Mutations ◽

Review Of The Literature ◽

Small Cell Lung ◽

Egfr Tyrosine Kinase Inhibitor ◽

Inhibitor Treatment ◽

Exon 19

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Case Report: Dacomitinib Overcomes Osimertinib Resistance in NSCLC Patient Harboring L718Q Mutation: A Case Report

Frontiers in Oncology ◽

10.3389/fonc.2021.760097 ◽

2021 ◽

Vol 11 ◽

Author(s):

Qian Shen ◽

Jingjing Qu ◽

Zhen Chen ◽

Jianying Zhou

Keyword(s):

Case Report ◽

Disease Progression ◽

Gamma Knife ◽

Parietal Lobe ◽

Brain Mri ◽

Gamma Knife Radiosurgery ◽

Small Cell ◽

Egfr Mutations ◽

Small Subset ◽

Small Cell Lung

BackgroundAdvanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations has been successfully treated with tyrosine kinase inhibitors (TKIs). However, resistance to osimertinib, a third-generation TKI, can be difficult to overcome in this small subset of patients and is attributed to secondary resistant mutations. Here, we report a case of acquired EGFR L858R/L718Q mutation with advanced NSCLC that resistant to osimertinib, which was successfully overcome using dacomitinib.Case PresentationA 64-year-old non-smoker woman was diagnosed with stage IV non-small cell lung adenocarcinoma with EGFR L858R mutation and brain metastasis in November 2018. Treatment with gefitinib and gamma knife radiosurgery was started as the first-line treatment. After 7 months, she experienced disease progression with increased primary lung lesions and switched to osimertinib based on an acquired EGFR T790M mutation. After another 4 months, the disease progressed, and she was switched to chemotherapy. During chemotherapy, brain MRI showed an increasing number of parietal lobe metastases. Hence, gamma knife radiosurgery was performed again. After 12 months, the disease progression resumed, and an EGFR L718Q mutation was found on biopsy. The patient was then challenged with dacomitinib, and the disease was partially responsive and under control for 6 months.ConclusionCurrently, there are no established guidelines for overcoming osimertinib resistance caused by the L718Q mutation. The acquired EGFR L718Q mutation in subsequent resistance to osimertinib could be overcome using dacomitinib, indicating a promising treatment option in the clinic.

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