Role of cMET expression in non-small cell lung cancer patients treated with EGFR tyrosine kinase inhibitors.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18092-e18092
Author(s):  
Hyun Chang ◽  
Xianglan Zhang ◽  
Da Rae Kim ◽  
Gun Min Kim ◽  
Se Hyun Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Small Cell Lung Cancer ◽  
Tumor Tissue ◽  
Kinase Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Nsclc Patients ◽  
Egfr Tkis

e18092 Background: We performed this study to investigate whether activation of cMET is associated with sensitivity to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC) patients. Methods: This retrospective study included 69 NSCLC patients with available tumor tissue, treatment response and survival data. cMET and hepatocyte growth factor (HGF) status was evaluated by immunohistochemistry. Results: A positive cMET, cMET[pY1003], cMET[pY1234/1235] and HGF were identified in 89%, 44%, 20% and 89% of cases, respectively. Positive cMET[pY1003] expression was associated with better objective response rate (OR) and clinical benefit rate (CBR) (OR, P = 0.033 and CBR, P = 0.039). Positive cMET[pY1234/1235] was significantly associated with a longer overall survival (OS) (P = 0.012) and time-to progression (TTP) (P = 0.031). Multivariable model confirmed that cMET[pY1234/235]-positive patients had a significant reduction in the risk of death and disease progression than cMET[pY1234/1235] –negative patients [OS; hazard ratio(HR)=0.29, P = 0.008 and TTP; HR=0.43; P=0.024] Conclusions: cMET expression in tumor tissue could be useful for predicting the clinical outcome of EGFR-TKIs treatment. Our results suggest that cMET expression in tumor tissue could be used to refine the selection of NSCLC patients expected to benefit from EGFR-TKIs treatment.

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.

BIM and SHP2 expression levels to predict clinical outcome to EGFR tyrosine kinase inhibitors (TKI) in EGFR-mutant non-small-cell lung cancer (NSCLC) patients (p).

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e19078-e19078
Author(s):  
Rosario Garcia Campelo ◽  
Teresa Moran ◽  
Felipe Cardenal ◽  
Guillermo Alonso-Jaudenes Curbera ◽  
Enric Carcereny Costa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Outcome ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Egfr Mutant ◽  
Nsclc Patients

scholarly journals Predictive molecular markers for EGFR-TKI in non-small cell lung cancer patients: new insights and critical aspects

2010 ◽  
Vol 1 (1) ◽  
pp. 10 ◽  
Author(s):  
Paola Ulivi ◽  
Daniele Calistri ◽  
Wainer Zoli ◽  
Dino Amadori
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Objective Response ◽  
Small Cell ◽  
Correct Selection ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Egfr Tkis

In recent years, a number of novel agents have been investigated that target specific molecular pathways in non-small cell lung cancer (NSCLC). A great deal of effort has been focused on identifying specific markers that predict treatment response, given that a tailored approach would maximize both the therapeutic index and the cost-effectiveness. The epidermal growth factor receptor (EGFR) pathway has emerged as a key regulator of cancer cell proliferation and invasion, and several specific EGFR inhibitors have been examined. Gefitinib and erlotinib are selective EGFR tyrosine kinase inhibitors (EGFR-TKIs), demonstrating good results in selected cases both in terms of objective response rate and of overall survival. At present, EGFR gene mutations are the best positive predictive factors for TKI therapy, and a number of other potential biomarkers are being investigated as additional positive or negative predictors of response. The correct selection of patients that could benefit from these innovative therapies, based on an accurate molecular characterization, is mandatory to provide the best clinical management. Currently, the main factor limiting the characterization of metastatic NSCLC patients is the small quantity of tumor cells available for molecular analysis. In this paper we provide an overview of the most important molecular predictive markers for EGFR-TKIs therapy in NSCLC patients, and focus attention on biological samples suitable for analysis and alternative sampling approaches such as plasma- or serum-derived DNA.

scholarly journals EGFR tyrosine kinase inhibitors for EGFR mutation-positive non-small-cell lung cancer: outcomes in Asian populations

2021 ◽  
Author(s):  
Edward S Kim ◽  
Barbara Melosky ◽  
Keunchil Park ◽  
Nobuyuki Yamamoto ◽  
James C-H Yang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Small Cell ◽  
Third Generation ◽  
Small Cell Lung ◽  
Asian Populations ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Egfr Tkis

Few data are available that have compared outcomes with different EGFR tyrosine kinase inhibitors (TKIs) specifically in Asian patients with EGFR mutation-positive non-small-cell lung cancer. In this narrative review, we have collated available data from prospective studies that have assessed first-, second- and third-generation EGFR TKIs in Asian populations, including subanalyses in individual countries (China and Japan). These data indicate that outcomes with first- and second-generation TKIs are broadly similar in Asian and non-Asian populations. However, while the third-generation EGFR TKI, osimertinib, confers significant overall survival benefit over erlotinib/gefitinib in non-Asians, this is not apparent in Asians, particularly in countries like Japan with well-resourced healthcare. Head-to-head comparisons of second- and third-generation EGFR TKIs, with OS as a primary end point, should be considered in Asia.

scholarly journals ID3021 Acquired resistance to with EGFR tyrosine kinase inhibitors by the EGFR T790M mutation in non-small cell lung cancer

2017 ◽  
Vol 4 (S) ◽  
pp. 33
Author(s):  
Van Thanh Ta
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Acquired Resistance ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Egfr Tkis

Mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene respond well to treatment with EGFR tyrosine kinase inhibitors (EGFR-TKIs) including gefitinib and erlotinib in non-small cell lung cancer (NSCLC). Detection of these mutations has an important role for therapeutic decision-making in NSCLC treatment. However, all patients who experienced marked improvements with these drugs eventually developed disease progression after 10-20 months of treatment due to the acquisition of drug resistance. Approximately half of the cases with acquired resistance to EGFR-TKIs can be accounted for by a second-site mutation in exon 20 of the EGFR kinase domain T790M. In this study, 40 patients with advanced NSCLC who developed acquired resistance to EGFR-TKIs were selected. The diagnosis was defined based on the Jackman criteria for acquired resistance to EGFR-TKIs in lung cancers. Re-biopsy were performed at National cancer hospital and Oncology hospitals at Ha Noi and Ho Chi Minh City. Scorpion ARMS method was used to detect EGFR mutation status. In all, 40% (16/40) of the patients carried T790M mutation after the failure of EGFR-TKIs. The study demonstrated a critical role of molecular diagnostics for TKI acquired resistance through re-biopsies at the time of disease progression.

scholarly journals Contribution of p53 in sensitivity to EGFR tyrosine kinase inhibitors in non-small cell lung cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sangyong Jung ◽  
Dong Ha Kim ◽  
Yun Jung Choi ◽  
Seon Ye Kim ◽  
Hyojeong Park ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Acquired Resistance ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
P53 Status ◽  
Egfr Tkis

AbstractThe emergence of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) with activating EGFR mutations is a major hindrance to treatment. We investigated the effects of p53 in primary sensitivity and acquired resistance to EGFR-TKIs in NSCLC cells. Changes in sensitivity to EGFR-TKIs were determined using p53 overexpression or knockdown in cells with activating EGFR mutations. We investigated EMT-related molecules, morphologic changes, and AXL induction to elucidate mechanisms of acquired resistance to EGFR-TKIs according to p53 status. Changes in p53 status affected primary sensitivity as well as acquired resistance to EGFR-TKIs according to cell type. Firstly, p53 silencing did not affect primary and acquired resistance to EGFR-TKIs in PC-9 cells, but it led to primary resistance to EGFR-TKIs through AXL induction in HCC827 cells. Secondly, p53 silencing in H1975 cells enhanced the sensitivity to osimertinib through the emergence of mesenchymal-to-epithelial transition, and the emergence of acquired resistance to osimertinib in p53 knockout cells was much slower than in H1975 cells. Furthermore, two cell lines (H1975 and H1975/p53KO) demonstrated the different mechanisms of acquired resistance to osimertinib. Lastly, the introduction of mutant p53-R273H induced the epithelial-to-mesenchymal transition and exerted resistance to EGFR-TKIs in cells with activating EGFR mutations. These findings indicate that p53 mutations can be associated with primary or acquired resistance to EGFR-TKIs. Thus, the status or mutations of p53 may be considered as routes to improving the therapeutic effects of EGFR-TKIs in NSCLC.

Predicting significance of EGFR mutation existing in tissues and plasma concuurrently or alone to EGFR–tyrosine kinase inhibitors (EGFR-TKIs) for advanced non-small cell lung cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19091-e19091
Author(s):  
Yuyan Wang ◽  
Jie Wang ◽  
Hua Bai ◽  
Zhijie Wang ◽  
Jianchun Duan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Small Cell ◽  
Small Cell Lung ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Egfr Tkis

e19091 Background: To investigate predicting significance of EGFR mutations existing in tissues couples with plasma or either sample alone to EGFR–tyrosine kinase inhibitors (EGFR-TKIs) treatment for advanced non–small-cell lung cancer (A-NSCLC). Methods: Two hundred-eighty-seven A-NSCLC patients met following criteria were included into this study: 1) had received EGFR-TKIs as first- or second-line therapy; 2) had sufficient tissue and plasma samples for EGFR mutation analysis. All patients were divided into four subgroups which were wild-type EGFR in both of specimens (B-/T-), mutated in both of specimens (B+/T+), mutated only in one specimen (B+/T- and B-/T+). EGFR mutation was screened by denaturing high performance liquid chromatograph (DHPLC) and confirmed by ARMS. Objective response rate (ORR) and progression-free survival (PFS) were compared among four subgroups. Results: Of all 287 patients, 101 patients carried EGFR mutation both in tissue and plasma, 103 patients carried mutation only in tissue (65 cases) or plasma (38 cases). Median PFS was 9.2 months (95% CI, 6.3 to 12.1) and 2.0 months (95% CI, 1.3 to 2.7) in B+/T+ and B-/T- group, respectively. For single mutated group, mPFS were 7.87 month for B-/T+ group (95% CI, 5.1 to 10.6) and 11.87 months for B+/T- group (95% CI, 3.3 to 20.5) (P=0.001). For ORR, 53.0% for B+/T+ group, 15.8% for B-/T- group, 40.0% for B-/T+ group and 28.9% for B+/T- group (P=0.000). EGFR-TKIs therapeutic line could not change trend which B+/T- or B+/T+ group had better PFS than B-/T+ group. Conclusions: Detection of EGFR mutation in tissue and plasma may have different significance in predicting response of EGFR-TKIs.

scholarly journals The Dynamic Use of EGFR Mutation Analysis in Cell-Free DNA as a Follow-Up Biomarker during Different Treatment Lines in Non-Small-Cell Lung Cancer Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Mónica Macías ◽  
Estibaliz Alegre ◽  
Gorka Alkorta-Aranburu ◽  
Ana Patiño-García ◽  
Beatriz Mateos ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Mutation Analysis ◽  
Tumor Tissue ◽  
Egfr Mutation ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Dna ◽  
Nsclc Patients ◽  
Egfr Tkis

Epidermal growth factor receptor (EGFR) mutational testing in advanced non-small-cell lung cancer (NSCLC) is usually performed in tumor tissue, although cfDNA (cell-free DNA) could be an alternative. We evaluated EGFR mutations in cfDNA as a complementary tool in patients, who had already known EGFR mutations in tumor tissue and were treated with either EGFR-tyrosine kinase inhibitors (TKIs) or chemotherapy. We obtained plasma samples from 21 advanced NSCLC patients with known EGFR tumor mutations, before and during therapy with EGFR-TKIs and/or chemotherapy. cfDNA was isolated and EGFR mutations were analyzed with the multiple targeted cobas EGFR Mutation Test v2. EGFR mutations were detected at baseline in cfDNA from 57% of patients. The semiquantitative index (SQI) significantly decreased from the baseline (median=11, IQR=9.5-13) to the best response (median=0, IQR=0-0, p<0.01), followed by a significant increase at progression (median=11, IQR=11-15, p<0.01) in patients treated with either EGFR-TKIs or chemotherapy. The SQI obtained with the cobas EGFR Mutation Test v2 did not correlate with the concentration in copies/mL determined by droplet digital PCR. Resistance mutation p.T790M was observed at progression in patients with either type of treatment. In conclusion, cfDNA multiple targeted EGFR mutation analysis is useful for treatment monitoring in tissue of EGFR-positive NSCLC patients independently of the drug received.

Immunotherapy in advanced non-small-cell lung cancer with EGFR mutations

Immunotherapy ◽  
2020 ◽  
Vol 12 (16) ◽  
pp. 1195-1207
Author(s):  
Fangfang Liu ◽  
Xun Yuan ◽  
Jizong Jiang ◽  
Qian Chu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Egfr Tkis

EGFR-tyrosine kinase inhibitors (EGFR-TKIs) had been regarded as the front-line treatment for advanced non-small-cell lung cancer (NSCLC) patients with EGFR mutations. However, resistance to EGFR-TKIs is inevitable, it remains a major challenge. Immune checkpoint inhibitors (ICIs) had shown superior clinical efficacy in many types of solid tumors, while it exhibited impaired overall efficacy in NSCLC with  EGFR mutations. In this review, we will perform a meta-analysis to assess the relationship between the programmed death ligand 1 (PD-L1) expression and clinical benefit of EGFR-TKIs. We also overview the immunotherapy in advanced NSCLC patients with EGFR mutations to investigate the potential biomarkers predicting the ICIs efficiency, and the subgroups that could benefit from ICIs treatment.

Sign in / Sign up

Export Citation Format

Share Document