scholarly journals Making the case for EGFR TKI sequencing in EGFR mutation-positive NSCLC: a GioTag study US patient analysis

2020 ◽  
Author(s):  
Bruce Feinberg ◽  
Balazs Halmos ◽  
Rasim Gucalp ◽  
Wenbo Tang ◽  
Barbara Moehring ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
De Novo ◽  
Growth Factor Receptor ◽  
T790m Mutation ◽  
Clinical Trial Registration ◽  
Evidence Based Treatment ◽  
Time To Treatment Failure ◽  
Epidermal Growth ◽  
Egfr Tki ◽  
Egfr T790m

Aim: To assess time-to-treatment failure (TTF) in US patients with epidermal growth factor receptor ( EGFR) mutation-positive non-small-cell lung cancer (NSCLC) who received sequential afatinib–osimertinib treatment in the global, observational GioTag study. Patients & methods: Patients had EGFR T790M mutation-positive disease after first-line afatinib and subsequently received osimertinib. The primary outcome was TTF. Results: In 129 patients at US centers, median TTF was 28.4 months (90% CI: 27.0–34.1). Median overall survival was 47.6 months (90% CI: 35.5–51.5). Conclusion: Sequential afatinib–osimertinib in this US-treated population was associated with long median TTF and represents an effective, evidence-based treatment option for US patients with EGFR mutation-positive NSCLC not presenting with active brain metastases or de novo T790M. Clinical Trial Registration: NCT03370770 (ClinicalTrials.gov)

scholarly journals Development of epidermal growth factor receptor tyrosine kinase inhibitors against EGFR T790M. Mutation in non small-cell lung carcinoma

Open Medicine ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. 68-77 ◽  
Author(s):  
Yuli Wang ◽  
Zhitao Guo ◽  
Yang Li ◽  
Qinghua Zhou
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Small Cell Lung Carcinoma ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Cell Lung Carcinoma ◽  
Epidermal Growth ◽  
Egfr T790m

AbstractIndividualized therapies targeting epidermal growth factor receptor (EGFR) mutations show promises for the treatment of non small-cell lung carcinoma (NSCLC). However, disease progression almost invariably occurs 1 year after tyrosine kinase inhibitor (TKI) treatment. The most prominent mechanism of acquired resistance involves the secondary EGFR mutation, namely EGFR T790M, which accounts for 50%–60% of resistant tumors. A large amount of studies have focused on the development of effective strategies to treat TKI-resistant EGFR T790M mutation in lung tumors. Novel generations of EGFR inhibitors are producing encouraging results in patients with acquired resistance against EGFR T790M mutation. This review will summarize the novel inhibitors, which might overcome resistance against EGFR T790M mutation.

Detection of EGFR mutations in NSCLC patients in clinical practice: Comparison between cobas and Scorpion ARMS method.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23101-e23101
Author(s):  
Natsuki Takano ◽  
Satoru Kitazono ◽  
Ryo Ariyasu ◽  
Junji Koyama ◽  
Masafumi Saiki ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Detection Rate ◽  
Egfr Mutation ◽  
Kinase Inhibitor ◽  
De Novo ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Detection Rates ◽  
Initial Biopsy ◽  
Egfr Tki

e23101 Background: Epidermal growth factor receptor (EGFR) mutation is the most important factor for determining the treatment strategy for non-small-cell lung cancers (NSCLCs). Currently, two methods (cobas and Scorpion ARMS) have been approved as companion diagnostics for using EGFR tyrosine kinase inhibitor (TKI). Although there are some differences in the spectrums and sensitivities for detecting EGFRmutations such as exon 19 deletions (ex19del), L858R and T790M mutations, the extent of the differences affecting clinical practice is unclear. Methods: All patients with NSCLC who underwent EGFR mutation tests and treated at our hospital from February 2014 to February 2016 were enrolled. To detect EGFR mutations, the Scorpion ARMS (S) method was used from 2014 to 2015 and thecobasEGFR Mutation Test (C) from 2015 to 2016. We retrospectively investigated the detection rate of each EGFRmutation type and compared the rates between the two methods. Results: A total of 1,287 patients were enrolled. To detect EGFR mutations, 627 patients were tested by the S method and 660 by the C method, respectively. Of 1287 patients, 910 patients underwent initial biopsy, whereas 121 patients underwent re-biopsy after EGFR-TKI failure. EGFRmutations were detected in 130 of 418 (31.1%) patients and 153 of 492 (31.1%) patients by the S and C methods, respectively in the initial biopsy (P = 0.982). However, the detection rate of ex19del was slightly lower in the S method (12.6%) than in the C method (16.3%) (P = 0.105). Conversely, the detection rate of L858R was lower in the C method (13.8%) than in the S method (16.7%), but the difference was not significant (P = 0.252). De novo T790M was detected in one (0.2%) patient by the S method and in none by the C method. In re-biopsy after EGFR-TKI failure, the detection rates of T790M were as follows: 19 of 55 patients (34.5%) by the S method and 20 of 66 (30.3%) by the C method (P = 0.619). Conclusions: The different spectrums and sensitivities of EGFR mutations between the S and C methods were observed; however, they did not significantly affect clinical practice.

scholarly journals Osimertinib in the treatment of patients with epidermal growth factor receptor T790M mutation-positive metastatic non-small cell lung cancer: clinical trial evidence and experience

2016 ◽  
Vol 10 (6) ◽  
pp. 549-565 ◽  
Author(s):  
Ivana Sullivan ◽  
David Planchard
Keyword(s):  
Lung Cancer ◽  
Clinical Trial ◽  
Epidermal Growth Factor Receptor ◽  
Resistance Mutation ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Epidermal Growth ◽  
Egfr T790m

Patients with advanced epidermal growth factor receptor ( EGFR) mutant non-small cell lung cancer (NSCLC) are particularly sensitive to treatment with first- or second-generation EGFR tyrosine kinase inhibitors such as gefitinib, erlotinib and afatinib, which block the cell-signaling pathways that drive the growth of tumor cells. Unfortunately, the majority of patients develop resistance to them after a median duration of response of around 10 months, and in over half of these patients the emergence of the EGFR T790M resistance mutation is detected. Osimertinib is an oral, highly selective, irreversible inhibitor of both EGFR-activating mutations and the T790M-resistance mutation, while sparing the activity of wild-type EGFR. This article reviews clinical trial development of osimertinib in patients with NSCLC, presenting efficacy and safety evidence for its value in the EGFR T790M mutation-positive population and in different settings, including patients with metastatic disease. The preclinical background of clinically acquired resistance to osimertinib is presented and the combination tactics being investigated in an attempt to circumvent this are addressed.

scholarly journals Efficacy and safety of first-line osimertinib treatment and postprogression patterns of care in patients with epidermal growth factor receptor activating mutation-positive advanced non-small cell lung cancer (Reiwa study): study protocol of a multicentre, real-world observational study

BMJ Open ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. e046451
Author(s):  
Kageaki Watanabe ◽  
Kiyotaka Yoh ◽  
Yukio Hosomi ◽  
Kazuhiro Usui ◽  
Go Naka ◽  
...  
Keyword(s):  
Real World ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Ethics Committee ◽  
Small Cell ◽  
Efficacy And Safety ◽  
Small Cell Lung ◽  
First Line ◽  
Epidermal Growth ◽  
Egfr Tki

IntroductionOsimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is widely used as the first-line treatment for EGFR mutation-positive non-small cell lung cancer (NSCLC). Nevertheless, most cases ultimately acquire resistance to osimertinib, and no effective treatment has been currently established for cases having progressive disease (PD) with osimertinib. In clinical practice, EGFR-TKI therapy could be continued beyond response evaluation criteria in solid tumours (RECIST)-defined PD cases when they are clinically stable. Currently, the progression pattern of osimertinib and criteria for identifying patients who might benefit from osimertinib beyond PD are unknown. In addition, the efficacy and safety of osimertinib as the first-line treatment in real-world clinical practice remain unclear in Japan. This multicentre study was designed to evaluate the real-world data on first-line osimertinib and its post-treatment.Methods and analysisThe study enrols patients with EGFR mutation-positive, advanced or recurrent NSCLC who received EGFR-TKI as the first-line therapy after 1 September 2018, from October 2019 to August 2020, and those started on osimertinib will be followed up until August 2022. We will evaluate the efficacy and safety of the first-line osimertinib treatment, adherence to it, progression patterns on RECIST PD and subsequent treatment.Ethics and disseminationAll participating patients will provide written informed consent before entering the study. The protocol, amendments and patients’ informed consent forms will be approved before study commencement by the institutional review board or independent ethics committee at each participation site (Lead Ethics Committee; Japan Red Cross Medical Center (26 April 2019, order number 976)). Patients will be anonymised before registration into the study and their anonymised data will be collected from the case report form. The results of this study will be presented at the national and international conferences and submitted for publication.Trial registration numberUMIN000038683.

scholarly journals De Novo T790M Mutation in an L858R Epidermal Growth Factor Receptor Mutant-Associated Lung Adenocarcinoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3074
Author(s):  
Takumi Fujiwara ◽  
Tetsu Kobayashi ◽  
Taro Yasuma ◽  
Corina N. D’Alessandro-Gabazza ◽  
Masaaki Toda ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
De Novo ◽  
Growth Factor Receptor ◽  
T790m Mutation ◽  
Epidermal Growth

Background: Lung cancer is the leading cause of mortality for cancer worldwide. A point mutation in exon 21 of the epidermal growth factor receptor resulting in the substitution of arginine for leucine at position 858 (L858R) is a frequent cause of lung adenocarcinoma. Tyrosine kinase inhibitors are effective for treating patients with lung cancer associated with mutant epidermal growth factor receptors but most tumors become resistant shortly after treatment. The substitution of methionine for threonine at position 790 (T790M) on exon 20 is the most frequently acquired mutation leading to resistance to tyrosine kinase inhibitors. Whether the T790M mutation occurred after tyrosine kinase inhibitor therapy or it already existed before therapy is unclear. Methods: Here, we developed mice with tetracycline-inducible lung-specific expression of the full-length genomic DNA of the human epidermal growth factor receptor containing an L858R mutation or both L858R and T790M mutations and evaluated de novo T790M mutation in untreated transgenic mice carrying a single L858R EGFR mutation. Results: The L858R mutation-associated lung adenocarcinoma acquired de novo T790 mutation without previous therapy. Conclusions: The results of this study suggest that lung tumors may spontaneously acquire T790M mutations without any drug-related selective pressure.

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