Detect T790M in cell free tumor DNA of Chinese advanced non-small cell lung cancer adenocarcinoma patients by different platforms and evaluate clinical outcomes of T790M positive patients with osimertinib monotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS9104-TPS9104
Author(s):  
Zhiyong Liang ◽  
Ying Cheng ◽  
Yuan Chen ◽  
Weiping Liu ◽  
You Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Digital Pcr ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Nsclc Patients ◽  
Egfr Tki ◽  
Tumor Dna ◽  
Egfr T790m

TPS9104 Background: EGFR T790M mutation occurs in approximately 50-60% of non-small cell lung cancer adenocarcinoma (NSCLC) patients with acquired EGFR-TKI resistance, based on tumor re-biopsies using an invasive clinical procedure. Recently, Cell free tumor DNA (ctDNA) has emerged as a specific and sensitive blood-based biomarker and studies have demonstrated ctDNA as a feasible and minimally invasive alternative to tissue biopsy. Data on different technology platforms used for EGFR T790M detection in blood in China is limited. We aim to compare the methods currently available in hospital practise, including cobas EGFR Mutation Test (Roche Molecular Systems), super-ARMS, digital PCR and NGS, to compare each platform and clinically validate each as companion diagnostic to osimertinib. Methods: This is an open-label, multi-center study in 250 locally advanced or metastatic NSCLC patients with documented EGFR sensitizing mutation and progression on previous EGFR-TKI. T790M mutation in plasma ctDNA will be tested by four methods: cobas, super-ARMS, digital PCR and NGS in order to evaluate the concordance, sensitivity and specificity of T790M testing in plasma between the cobas test and the other platforms. T790M positive patients by any of the four platforms will receive osimertinib treatment (administered orally as one 80 mg tablet once a day in ASTRIS study, NCT02474355) and the clinical outcomes (PFS, ORR, OS) will be followed. Patients will continue to receive osimertinib until disease progression (PD), as assessed by investigators. Digital PCR and NGS will be used to monitor the molecular evolution of T790M and C797S in plasma from NSCLC patients during osimertinib treatment. NGS will also be used to explore acquired resistance mechanisms before osimertinib treatment and after PD. 23 of planned 250 patients have been enrolled in the study as of January 2017. Clinical trial information: NCT02997501.

scholarly journals Clinical Characteristics of Osimertinib Responder in Non-Small Cell Lung Cancer Patients with EGFR-T790M Mutation

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 365 ◽  
Author(s):  
Akihiro Yoshimura ◽  
Tadaaki Yamada ◽  
Naoko Okura ◽  
Takayuki Takeda ◽  
Kazuki Hirose ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Nsclc Patients ◽  
Egfr T790m ◽  
Egfr Tkis

Osimertinib is a mutant-selective EGFR inhibitor that is effective against non-small cell lung cancer (NSCLC) in patients with the EGFR-T790M mutation, who are resistant to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, the factors affecting response to osimertinib treatment are unknown. In this retrospective study, 27 NSCLC patients with the EGFR-T790M mutation were enrolled at five institutions in Japan. Among several parameters tested, the progression-free survival (PFS) associated with the initial EGFR-TKIs was positively correlated with the PFS after osimertinib treatment (p = 0.021). The median PFS following osimertinib treatment and the overall survival (OS) were longer in patients who responded to osimertinib than in those who did not (17.7 months versus 3.5 months, p = 0.009 and 24.2 months versus 13.5 months, p = 0.021, respectively). A multivariate analysis demonstrated that the PFS with initial EGFR-TKIs was significantly related to the PFS with osimertinib treatment (p = 0.035), whereas osimertinib response was significantly related to the PFS and OS with osimertinib treatment (p = 0.016 and p = 0.006, respectively). Our retrospective observations indicate that PFS following the initial EGFR-TKI treatment and the response rate to osimertinib might be promising predictors for effective osimertinib treatment in NSCLC patients with the EGFR-T790M mutation.

Effect of metformin on the effects of TKI on human lung carcinoma cells harboring KRAS or EGFR-T790M mutation.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18051-e18051
Author(s):  
Yongsheng Wang ◽  
Yu Ma ◽  
Dan Li ◽  
Fuchun Guo
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Dependent Manner ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Tki Resistance ◽  
Egfr Tki ◽  
Egfr T790m

e18051 Background: K-ras and egfr-T790M mutation show primary and acquired resistance to EGFR-TKI in non-small cell lung cancer, respectively. The antidiabetic drug metformin has been associated with a decreased incidence and a better prognosis of lung cancer. The affects of metformin on the EGFR-TKI resistance in non-small cell lung cancer remain unknown. Methods: The effects of metformin on EGFR-TKI were investigated in k-ras mutant A549 cells, and egfr-T790M mutant H1975 cells both in virto and in vivo. The proliferation and apoptosis were tested. The underlying mechanisms were also analyzed. Results: Our data showed metformin significantly enhanced the inhibition activity of gefitinib both in A549 and H1975 cells in vitro. At the molecular level, metformin inhibited multiple signaling including LKB1-AMPK-S6K, PI3K-AKT and Raf-MEK-MAPK in a dose-dependent manner. Furthermore, the increased tumor inhibitions were observed in nude mice models of A549 (P<0.05)and H1975 (P<0.01). Conclusions: Metformin can increase the effects of EGFR-TKI in lung adenocarcinoma harboring K-ras and egfr-T790M mutation. Our study may provide a new strategy to overcome the EGFR-TKI resistance in NSCLC.

The ability of avitinib to penetrate the blood brain barrier and its control of intra-/extra- cranial disease in patients of non-small cell lung cancer (NSCLC) harboring EGFR T790M mutation.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20613-e20613 ◽  
Author(s):  
Hanping Wang ◽  
Li Zhang ◽  
Xin Zheng ◽  
Xiaotong Zhang ◽  
Xiaoyan Si ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Blood Brain Barrier ◽  
Cell Lung Cancer ◽  
Penetration Rate ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Nsclc Patients ◽  
Egfr T790m

e20613 Background: Avitinib is an oral, potent, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor selective for T790M resistance mutations. We report the safety, the intracranial/extracranial efficacy, and the blood brain barrier (BBB) penetration rate of Avitinib in non-small cell lung cancer(NSCLC) patients with EGFR T790m mutation. The data come from Peking Union Medical College hospital-a single center of the Phase I, open-label, multicenter study (NCT02330367). Methods: NSCLC Patients with acquired EGFR T790m (+) were enrolled. Patients were orally administered with dose escalating from 150 mg to 300 mg twice daily for 28-continuous-day cycles until disease progression. Blood (2mL) and cerebrospinal fluid (CSF) samples (2ml) were collected for concentration analysis on day 29 in available patients with brain metastases (BM). Tumor response was assessed on day 29 and then every 8 weeks. Results: Sixteen patients were included. Nine patients had asymptomatic BM. The most frequent adverse events were the elevated hepatic transaminases (10/16, 62.5%) and diarrhea (5/16, 31.3%), Most were mild and reversible. 9 Patients (56.3%) achieved Partial Response (PR), 6 (37.5%) achieved Stable Disease (SD). Median Progress Free Survival (PFS) was 253 days (95%CI: 154.8-339.2). Of the 8 evaluable BM patients, intracranial PFS were shorter than extracranial in only two patients. The blood and CSF analysis of 6 BM patients showed the BBB penetration rate were 0.046%-0.146% (Table). Conclusions: Avitinib is well tolerated and efficacious in EGFR T790m(+) NSCLC patients. Its concentration in CSF is low, and the penetrability of BBB is weak. But it still showed a good control of BM. Further studies are proceeding. Clinical trial information: NCT02330367. [Table: see text]

Effect of uncommon and insensitive mutation on EGFR-TKI in treatment of non-small cell lung cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21652-e21652
Author(s):  
Hui Zhang ◽  
Da Jiang ◽  
Suju Wei ◽  
Yanzhi Cui ◽  
Ying Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Mutation Frequency ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Egfr Tki ◽  
Egfr T790m ◽  
Egfr Tkis

e21652 Background: EGFR-TKI application is directed by the situation of mutations of epidermal growth factor receptor, in addition, the mutations of ALK, ROS-1,C-met, BRAF, Her-2, RET,NTRK1, PI3K, MEKI have potential effects on guiding treatment. This study aimed to investigate the uncommon and insensitive mutations and their effect on prognosis in non-small cell lung cancer (NSCLC) patients treated with EGFR-TKI. Methods: 21 NSCLC patients treated with EGFR-TKIs were enrolled, 9 with Gefitinib, 5 with Osimertinib and 7 with Icotinib. All patients were detected with targeted NGS 1000 gene panel. Afterwards, the EGFR sensitive mutation, uncommon mutation and mutations accompanied EGFR T790M were analyzed. Furthermore, the correlations of gene mutation with metastasis, OS and PFS were analyzed. SPSS 21.0 was used for statistical analysis, t test for continuous variables and χ2 test for classified variables. Results: In all the patients, EGFR p.[T790M] and p.[L858R] mutations were detected in 4.76% and 23.81% of the patients, respectively. In the 5 patients treated with Osimertinib, one had EGFR p.[T790M] mutation and curative effects was stable disease (SD). The mutations accompanied EGFR T790M included SMARCA4 p.[K1390Q] (2.23%), DNMT3A p.[F755S] (2.17%), MTOR p.[Y1450*] (2.15%), TPMT p.[L182R] (1.84%), etc. For the other four patients treated with Osimertinib, two of them were partial response (PR) and two were SD, accompanied with mutations such as EGFR p.[L858R] (55.00%), ARID1A p.[P16del] (2.83%), TP53 p.[R248W] (21.73%) and AR p.[Q60L] (4.24%). In addition, among all the mutations, 18 uncommon mutations were detected, in which ATM (23.26%), AR (23.26%) and MTOR (37.21%) were markedly associated with OS. Besides, the mutation frequency of 67 genes, such as ABCG2, AURKA, EPHA3 and ATR were correlated with OS. The mutation frequency of FGFR1 was significantly different between the patients with and without metastasis. The mutations of 22 genes, for instance ABCG2 p.[P21L], FAT1 p.[L398F], GNAS p.[F226V] and KMT2C p.[N2842Ilefs], were correlated with PFS during the treatment. Conclusions: EGFR-TKI has similar curative effects in EGFR p.[T790M] negative patients. Gene mutations, including uncommon mutations and EGFR insensitive mutations, can significantly affect the prognosis in NSCLC patients treated with EGFR-TKIs.

scholarly journals EP1.01-63 The Usefulness of “Serum” Samples to Detect EGFR T790M Mutation in EGFR-TKI-Resistant Non-Small Cell Lung Cancer

2019 ◽  
Vol 14 (10) ◽  
pp. S936-S937
Author(s):  
K. Kobayashi ◽  
K. Naoki ◽  
S. Ikemura ◽  
H. Yasuda ◽  
I. Kawada ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Serum Samples ◽  
T790m Mutation ◽  
Egfr Tki ◽  
Egfr T790m
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