scholarly journals P2.03-040 EGFR T790M Mutation Detection and Osimertinib Treatment Response Evaluation by Liquid Biopsy in Advanced NSCLC Patients

2017 ◽  
Vol 12 (11) ◽  
pp. S2142-S2143 ◽  
Author(s):  
C. Li ◽  
H. Liu ◽  
B. Zhang ◽  
Z. Zhang ◽  
Y. Su ◽  
...  
2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20524-e20524
Author(s):  
Francesca Zanelli ◽  
Maria Pagano ◽  
Candida Bonelli ◽  
Bruno Casali ◽  
Alberto Cavazza ◽  
...  

e20524 Background: over the past decade, personalized management based on the molecular features of tumours in patients with advanced non small-cell lung cancer (NSCLC) has entered routine clinical practice. The poor performance of many advanced NSCLC patients may limit invasive biopsies. The liquid biopsy is a diagnostic procedure performed on cancer-derived material obtained in blood samples. In this abstract, we will describe our experience with liquid biopsies. Methods: In the Reggio Emilia Clinical Cancer Centrefrom March 2016 to December 2016, 42 patients with advanced NSCLC were analyzed that had had or had already started first line therapy. The liquid biopsy was repeated at each imaging response evaluation by thoracic-abdominal compound tomography (CT) scan performed every 3 months. In the liquid biopsy, the mutational status of EGFR was analyzed with real time PCR (KIT cobas EGFR mutation test v2 CE-IVD Roche); in tissue, it was evaluated by pyrosequencing. Results: 21/42 liquid biopsies were EGFR-mutated (12/21 eson 19 and 9/21 eson 21). In 3/21 (14.3%) cases, the tissue biopsies showed wild type (WT) EGFR. 6 liquid biopsies were also performed at time 0 (diagnosis). All liquid biopsies of EGFR WT remained WT during treatment and imaging evaluation. The median number of liquid biopsy tests for patients was 2 (range 1-3). In 4/21 cases, T790M was performed: 3 cases in both liquid biopsies and tissue, and 1 case in tissue but not in liquid biopsy. TKi therapy was ineffective in this patient with T790M mutation detected in tissue, but not in liquid biopsy. In all patients, the disappearance of the T790M mutation during TKi therapy was related to disease progression. In 11 cases, modification of EGFR mutation status during treatment anticipated CT scan evidence of disease progression (median = three months). Conclusions: the liquid biopsy is an excellent resource. In our experience the liquid biopsy is the sensitive method of choice during treatment of advanced NSCLC patients. EGFR modification status during TKi therapy showed advanced disease progression.


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

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21563-e21563
Author(s):  
Jiangtao Cheng ◽  
YiHui Yao ◽  
Yu-Er Gao ◽  
Shi-Ling Zhang ◽  
Hua-Jun Chen ◽  
...  

e21563 Background: Osimertinib is standard of care for patients with advanced non–small-cell lung cancer (NSCLC) carrying acquired epidermal growth factor receptor ( EGFR) T790M mutation. However, few studies have been conducted to investigate the impact of rebiopsy on clinical outcomes after resistance to osimertinib. We evaluated whether next-generation sequencing (NGS) of tissue and liquid rebiopsy could favor post-progression outcomes of T790M-positive advanced NSCLC patients treated with osimertinib. Methods: Immediately just after resistance to second- or further-line osimertinib, advanced NSCLC patients with acquired EGFR T790M mutation were retrospectively divided into the NGS and non-NGS groups according to whether they underwent NGS of tissue or liquid rebiopsy. The co-primary endpoints were post-progression survival (PPS) defined as the time from osimertinib resistance to subsequent-line treatment resistance, and post-progression overall survival (pOS) defined as from osimertinib resistance to death or end of the last follow-up. Multivariable analyses were done using Cox proportional hazards regression model and log-rank test. Results: Between January 2017 and July 2019, 89 patients (62 vs. 27 for the NGS and non-NGS groups respectively) were eligible for final analyses. In the NGS group, 3.2% (2/62) underwent tissue rebiopsy only, 29.0% (18/62)only had liquid rebiopsy, and 66.8% (42/62)with both tissue and liquid rebiopsy.The NGS group received more targeted or combined therapy after resistance to osimertinib (62.9% vs. 40.8%, P= 0.053). The NGS group was significantly superior to the non-NGS group in the co-primary endpoints. The median PPS was 6.1 vs. 2.7 months (hazard ratio [HR], 0.49; 95%CI, 0.30 to 0.80; 2-sided log-rank P= 0.004). Meanwhile, the median pOS was 11.7 vs. 6.8 months (HR, 0.50; 95%CI, 0.29 to 0.85, 2-sided log-rank P= 0.009). Conclusions: Providing more opportunities for individualized treatment, NGS of tissue and liquid rebiopsy favors post-progression outcomes of EGFR T790M-positive advanced NSCLC patients treated with osimertinib.


2016 ◽  
Vol 69 ◽  
pp. S3
Author(s):  
E. Castellanos-Rizaldos ◽  
D.G. Grimm ◽  
V. Tadigotla ◽  
S. Bentink ◽  
J. Hurley ◽  
...  

2021 ◽  
Author(s):  
You-Lung Chang ◽  
Yen-Fu Chen ◽  
Ying-Yin Chen ◽  
Shih-Chieh Chang ◽  
Cheng-Yu Chang ◽  
...  

Abstract Backgrounds: Astrocyte-elevated gene-1 (AEG-1) functions as an oncogene and regulates angiogenesis in non-small cell lung cancer (NSCLC). In this prospective study, we assessed the values of plasma AEG-1 mRNA expression by liquid biopsy associated with tumor response and survival in NSCLC patients treated with pemetrexed. Methods: Patients diagnosed advanced NSCLC were enrolled to be treated with pemetrexed combined platinum as first-line chemotherapy. All patients underwent blood sampling before any cancer treatment (C0) and at first response evaluation after two cycles (C2) treatments. Response to chemotherapy and survival were assessed. Plasma mRNA was extracted from peripheral blood mononuclear cell (PBMC) and quantification of RNA was performed by real-time PCR.Results: A total of 50 patients with advanced NSCLC were included and 13 of 50 patients combined with bevacizumab. In patient groups of SD (n = 13) and PD (n = 10), the plasma mRNA of AEG-1, thymidylate synthase (TS) and CK19 were elevated significantly at C2 compared to patients in treatment response group (PR, n = 27) (PR v.s. SD or PD, AEG-1: 1.22 ± 0.80 v.s. 4.51 ± 15.45, p = 0.043). NSCLC patients had elevated AEG-1 (AEG-1 ≥ 2) after 2-cycle chemotherapy had shorter PFS and OS (high AEG-1 v.s. low AEG-1, median, PFS: 5.5 v.s. 11.9 months, p = 0.021; OS: 25.9 v.s. 40.8 months, p = 0.019, respectively). In Cox regression analysis, increased plasma mRNA expression of AEG-1indicated poor prognosis in survival.Conclusion: Circulating mRNA concentration of AEG-1 could be a predictive and prognostic biomarker in NSCLC patients treated with pemetrexed. Increased expression of AEG-1 contributed to the chemoresistance and caused lung cancer progression.


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.


Sign in / Sign up

Export Citation Format

Share Document