Noninvasive monitoring of dynamics of acquired EGFR-T790M mutation and discovery of its heterogeneity in patients with advanced NSCLC treated with EGFR-TKI.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 11049-11049
Author(s):  
Di Zheng ◽  
Xin Ye ◽  
Yun Sun ◽  
Meizhuo Zhang ◽  
Jiying Wang ◽  
...  
2020 ◽  
Author(s):  
Qianqian Wang ◽  
Wen Gao ◽  
Fangyan Gao ◽  
Shidai Jin ◽  
Tianyu Qu ◽  
...  

Abstract Background To compare the benefits and explore the cause of acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and its combination with chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients harboring EGFR mutation in a real-life setting.Methods This retrospective analysis included 117 advanced NSCLC patients with EGFR mutation who underwent next-generation sequencing (NGS) prior to treatment. The combination group included 50 patients who received the regimen of EGFR-TKI combined with chemotherapy, while the EGFR-TKI monotherapy group included 67 patients treated with TKI only. The primary endpoint of this study was progression-free survival (PFS); the secondary endpoints were overall survival (OS), response rate, and toxicity.Results The median PFS was significantly longer in the combination group than in the EGFR-TKI monotherapy group (19.00 months [95% CI, 14.674-23.326] vs. 11.70 months [95% CI, 10.807-12.593], p = 0.000). Subgroup analysis showed a similar trend of results. The median OS was not reached in the combination group and was 38.50 (95% CI, 35.300-41.700) months in the EGFR-TKI monotherapy group (p = 0.586). Patients in the combination group were more likely to experience adverse events, most of which showed the severity of grade 1 or 2. T790M mutation remains the main reason for acquired resistance, and the frequency of T790M mutation was similar between the two groups (p = 0.898). Conclusions Compared with EGFR-TKI monotherapy, EGFR-TKI combined with chemotherapy significantly improved PFS in advanced NSCLC patients with EGFR mutation, with acceptable toxicity.


2020 ◽  
Author(s):  
Bruce Feinberg ◽  
Balazs Halmos ◽  
Rasim Gucalp ◽  
Wenbo Tang ◽  
Barbara Moehring ◽  
...  

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)


Lung Cancer ◽  
2020 ◽  
Vol 139 ◽  
pp. 133-139 ◽  
Author(s):  
Shuo Yang ◽  
Shiqi Mao ◽  
Xuefei Li ◽  
Chao Zhao ◽  
Qian Liu ◽  
...  

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 8080-8080
Author(s):  
Di Zheng ◽  
Xin Ye ◽  
Meizhuo Zhang ◽  
Yun Sun ◽  
Jiying Wang ◽  
...  

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18051-e18051
Author(s):  
Yongsheng Wang ◽  
Yu Ma ◽  
Dan Li ◽  
Fuchun Guo

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.


2018 ◽  
Vol 13 (9) ◽  
pp. S166-S167
Author(s):  
M.C. Mosqueira ◽  
S. Anchordoqui ◽  
R. Martínez Correa ◽  
E. Pichelbauer ◽  
A. Trinchero ◽  
...  

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