Nachweis einer T790M Mutation im Pleuraerguss unter Therapie mit Erlotinib als Hinweis auf Tumorprogress bei Nachweis einer Exon19 Mutation im EGFR-Gen im Tumorgewebe

Pneumologie ◽  
2011 ◽  
Vol 65 (S 01) ◽  
Author(s):  
C Schumann ◽  
S Rüdiger ◽  
T Wibmer ◽  
M Lanzinger ◽  
K Stoiber ◽  
...  
Keyword(s):  
T790m Mutation

PREDICTIVE VALUE OF THE DYNAMIC DETERMINATION OF CIRCULATING TUMOR DNA ON PFS IN PATIENTS WITH EGFR MUTATED NSCLC, WITH OSIMERTINIB THERAPY

2020 ◽  
Vol 66 (2) ◽  
pp. 135-142
Author(s):  
Fedor Moiseenko ◽  
Mariya Stepanova ◽  
Nikita Volkov ◽  
Albina Zhabina ◽  
A. Myslik ◽  
...  
Keyword(s):  
Predictive Value ◽  
Molecular Genetic ◽  
Predictive Marker ◽  
Circulating Tumor Dna ◽  
Qualitative Assessment ◽  
Genetic Profile ◽  
T790m Mutation ◽  
Rare Mutations ◽  
Effect Of Therapy ◽  
Pcr Method

Aim: study of the predictive value of determining ctDNA during treatment with osimertinib in patients with NSCLC with EGFR mutation. Methods: The study included patients with metastatic EG-FR-associated NSCLC, in whom, with progression against the background of 1st - 2nd generation TKIs, the T790M mutation was detected. Patients received osimertinib therapy 80 mg/ day, daily, until progression. Before treatment, and then every 2 months, whole blood was taken to conduct a qualitative assessment of ctDNA in dynamics by the RT-PCR method. Results: From 2016 to 2019 in St. Petersburg Clinical Scientific and Practical Center of Specialized Types of Medical Care (Oncology), 22 patients were identified T790M associated progression of EGFR NSCLC. 81.9% (18/22) are women, 18.1% (4/22) are men. The average age is 61.2 years (50-75). 1/22 had smoking experience for more than 30 years. The molecular genetic profile in 16 is represented by ex19del, 5 L858R, 1 -a combination of rare mutations G719S+S768I. The effect of therapy was evaluated in 20/22 patients. PR and SD were registered in 9/20 (45%) and 10/20 (50%) patients, respectively. Median PFS - 16.7 months (cI 95%, 11,4-22,0). In 12/22 patients was observed the disappearance of ctDNA T790M after 2 months of osimertinib therapy. PFS is 18,9 months (95% CI, 14,8-19,7), in patients with no mutation detected in the second month of treatment compared with the group of patients in which the ctDNA was determined (PFS 8.0 months) (CI 95%, 4,2-11,8) (p=0.015). Correlation analysis did not reveal any clinical factors associated with the disappearance of ctDNA. Conclusions: The disappearance of ctDNA in plasma after 2 months of treatment with osimertinib is associated with an increase in PFS and can be considered as a predictive marker in patients with metastatic NSCLC EGFR T790M.

scholarly journals High expression of hypoxia inducible factor 1α related with acquired resistant to EGFR tyrosine kinase inhibitors in NSCLC

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Qian Jin ◽  
Feihua Huang ◽  
Xianrong Xu ◽  
Haidong He ◽  
Yingqing Zhang
Keyword(s):  
First Generation ◽  
Kinase Inhibitors ◽  
Acquired Resistance ◽  
Hypoxia Inducible Factor ◽  
High Expression ◽  
Normal Lung ◽  
Nsclc Tissue ◽  
T790m Mutation ◽  
Level Group ◽  
Egfr Tkis

AbstractThe acquired resistance of the first generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is a main factor leading to poor prognosis of non-small cell lung cancer (NSCLC), so we researched whether the high expression of hypoxia-inducible factor-1α (HIF-1α) in EGFR-TKIs sensitive NSCLC tissue tends to induce the acquired resistance. We detected the HIF-1α in normal lung tissue, EGFR-TKIs sensitive NSCLC tissue, the first generation EGFR-TKIs acquired resistant NSCLC tissue and acquired EGFR T790M mutation NSCLC tissue with the method of immunohistochemistry. Then, we compared the expression of HIF-1α in these tissues, and evaluate the effect of HIF-1α expression to the occurrence of acquired resistance. The expression of HIF-1α was much higher in the EGFR-TKIs sensitive NSCLC tissue than that in normal lung tissue. HIF-1α level became higher after the occurrence acquired resistance. There was negative correlation between HIF-1α level before receiving treatment and the time of acquired resistance occurring as well as the acquired EGFR T790M mutation occurring. As the treatment going on, EGFR-TKIs sensitivity rate of low HIF-1α level group was much higher than that of high level group. The high expression of HIF-1α related with the acquired resistance of the first generation EGFR-TKIs, and HIF-1α can be a biomarker to predict the early occurrence of acquired resistance.

scholarly journals Real-world osimertinib for EGFR mutation-positive non-small-cell lung cancer with acquired T790M mutation

2020 ◽  
Vol 16 (21) ◽  
pp. 1537-1547
Author(s):  
Fumio Imamura ◽  
Madoka Kimura ◽  
Yukihiro Yano ◽  
Masahide Mori ◽  
Hidekazu Suzuki ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Acquired Resistance ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Clinical Trial Registration

Aim: Osimertinib is a key drug for EGFR mutation-positive non-small-cell lung cancer (NSCLC). As the hazards ratio of overall survival in comparison with first-generation EGFR-tyrosine kinase inhibitors was almost similar between FLAURA and ARCHER 1050, salvage use of osimertinib is still a treatment option. Patients & methods: We retrospectively analyzed the clinical courses of EGFR mutation-positive NSCLC patients who were potential candidates for salvage osimertinib. Results: Among 524 patients enrolled from five hospitals, 302 patients underwent biopsy, with 52.6% detection rate of T790M. Osimertinib was administered in 93.6% of the T790M-positive patients. The overall response rate and median progression-free survival time of osimertinib were calculated with 147 patients, to be 55.6% and 17.2 months, respectively. Conclusion: Osimertinib is active for T790M-driven acquired resistance in EGFR-mutant NSCLC, but the detection of T790M was unsatisfactory. Clinical Trial Registration: UMIN000028989 (UMIN Clinical Trials Registry)

Re-use of erlotinib in a patient using osimertinib after erlotinib, case report

2021 ◽  
pp. 107815522110191
Author(s):  
Pinar Gursoy
Keyword(s):  
Lung Cancer ◽  
Case Report ◽  
Treatment Options ◽  
Resistance Mutation ◽  
Growth Factor Receptor ◽  
Complete Response ◽  
Egfr Mutations ◽  
T790m Mutation ◽  
Development Of Resistance ◽  
Exon 19

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.

scholarly journals Diagnostic accuracy of droplet digital PCR for detection of EGFR T790M mutation in circulating tumor DNA

2018 ◽  
Vol Volume 10 ◽  
pp. 1209-1218 ◽  
Author(s):  
Rui Zhang ◽  
Bojiang Chen ◽  
Xiang Tong ◽  
Ye Wang ◽  
Chengdi Wang ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Droplet Digital Pcr ◽  
T790m Mutation ◽  
Tumor Dna ◽  
Egfr T790m

Chitosan-derived Nanoparticles Impede Signal Transduction for T790M Lung Cancer Therapy

2021 ◽  
Author(s):  
Guojun Huang ◽  
Qi Chen ◽  
Jiawei Hu ◽  
Jianming Mao ◽  
Yunhong He ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Receptor Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
T790m Mutation ◽  
Develop Disease Progression ◽  
Lung Cancer Therapy ◽  
Epidermal Growth ◽  
Egfr Tkis ◽  
Receptor Tyrosine Kinase Inhibitors

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treated patients ultimately develop disease progression, about 50% of which involved in the emergence of a T790M mutation acquiring drug resistance. In...

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