scholarly journals Liquid-Biopsy-Based Identification of EGFR T790M Mutation-Mediated Resistance to Afatinib Treatment in Patients with Advanced EGFR Mutation-Positive NSCLC, and Subsequent Response to Osimertinib

2018 ◽  
Vol 14 (1) ◽  
pp. 75-83 ◽  
Author(s):  
Maximilian J. Hochmair ◽  
Anna Buder ◽  
Sophia Schwab ◽  
Otto C. Burghuber ◽  
Helmut Prosch ◽  
...  
Author(s):  
Giovanni Gancitano ◽  
Roberto Ravasio ◽  
Lorenzo Cattelino ◽  
Paolo Di Procolo ◽  
Diego Cortinovis

BACKGROUND: A histopathological and mutational diagnosis has become a priority in the correct choice of the most appropriate cancer therapy for NSCLC. In the absence of a molecular analysis, the therapeutic choice will be directed towards platinum-based chemotherapy, thus preventing, in the presence of a specific mutation, the benefits deriving from the administration of a target therapies (TT).AIM: the present analysis was carried out with the aim of estimating the clinical impact, expressed in terms of progression free survival (PFS), associated with the use of the combined strategy (tissue biopsy and liquid biopsy) or the tissue strategy in the EGFR+ mNSCLC population.METHODS: A pre-existing cost-consequence model was adapted to estimate the annual number of mNSCLC patients with or without the EGFR mutation in order to decide the oncological treatment to be administered in first (1L) or second line (2L). In 1L, against the presence of the EGFR mutation, the administration of a Tyrosine Kinase Inhibitor (TKI), such as osimertinib, gefitinib, erlotinib or afatinib, was considered; in the absence of the EGFR mutation, the administration ofstandard platinum-based chemotherapy was instead considered. With reference to 2L, in the presence of the EGFR T790M mutation, only osimertinib was considered. In the absence of the EGFR T790M mutation, the administration of the standard platinum-based chemotherapy was also considered. The PFS data associated with each of the drugs considered were extrapolated from the respective clinical studies. Key variables were tested in the sensitivity analysis.RESULTS: The adoption of the combined strategy (tissue biopsy and liquid biopsy), by virtue of a greater number of patients treated with TKIs, would make it possible to increase the average PFS in the range of 1.1-3,7 months in the 1L and by 1.4 months in the 2L.CONCLUSION: These results show how the adoption of a correct diagnostic strategy is critical in order to optimize the choice of the therapeutic path in the 1L and 2L of mNSCLC. The addition of the liquid biopsy to the classic diagnostic path (tissue biopsy) would in fact allow to obtain an increase in therapeutic efficacy (average PFS).


2017 ◽  
Vol 12 (11) ◽  
pp. S2133
Author(s):  
T. Sakamoto ◽  
K. Yamane ◽  
N. Tanaka ◽  
M. Yanai ◽  
H. Izumi ◽  
...  

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)


2019 ◽  
Vol 82 (6) ◽  
pp. 473-476 ◽  
Author(s):  
Hsiang-Ling Ho ◽  
Chao-Cheng Huang ◽  
Wen-Hui Ku ◽  
Chung-Liang Ho ◽  
Chia-Hung Lin ◽  
...  

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 ◽  
...  

2017 ◽  
Vol 12 (11) ◽  
pp. S2137 ◽  
Author(s):  
M. Hochmair ◽  
S. Schwab ◽  
O. Burghuber ◽  
R. Koger ◽  
U. Setinek ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Liang Shi ◽  
Junfang Tang ◽  
Hong Tao ◽  
Lili Guo ◽  
Weihua Wu ◽  
...  

BackgroundWe aimed to investigate the feasibility of detecting epidermal growth factor receptor (EGFR) mutations in cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) and plasma of advanced lung adenocarcinoma (LADC) with brain metastases (BMs) by droplet digital polymerase chain reaction (ddPCR).MethodsThirty advanced LADC patients with BMs were enrolled, and their matched CSF and plasma samples were collected. Droplet digital PCR was used to test cfDNA in CSF and plasma for EGFR mutation status. The clinical response and prognosis were evaluated.ResultsOut of 30 patients, there were 21 females and 9 males, aged 34-75 years. In all of the cases, CSF cytology were negative. In ddPCR assays, 10 patients (33.3%) had EGFR mutation in CSF, including 3 cases of EGFR T790M mutation, and 16 patients (53.3%) had EGFR mutation in plasma, including 6 cases of EGFR T790M mutation. Five patients with activating EGFR mutations in CSF achieved an intracranial partial response (iPR) after combination treatment with the first-generation EGFR-tyrosine kinase inhibitors. Three patients with EGFR T790M mutations in CSF achieved iPR after second-line osimertinib treatment. The median overall survival and intracranial progression-free survival were 17.0 months and 11.0 months, respectively.ConclusionIt was feasible to test EGFR mutation in cerebrospinal fluid and plasma. In LADC patients with brain metastasis, cerebrospinal fluid can be used as a liquid biopsy specimen to guide treatment strategy by monitoring EGFR mutation status.


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