Plasma microRNA signatures to predict EGFR-TKI resistance in EGFR-mutant advanced NSCLC patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19136-e19136
Author(s):  
Shuhang Wang ◽  
Jie Wang ◽  
Hua Bai ◽  
Tongtong An ◽  
Jun Zhao ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Training Group ◽  
Deletion Mutation ◽  
Resistant Group ◽  
Plasma Microrna ◽  
Different Response ◽  
Nsclc Patients ◽  
Egfr Tki ◽  
Egfr Tkis

e19136 Background: EGFR mutation is a strong predictor of EGFR-TKIs (epidermal growth factor receptor tyrosine kinase inhibitor) therapy in advanced NSCLC. However, 20-30% of patients with EGFR mutation are resistant to EGFR-TKIs, suggesting that other determinants of outcome beyond EGFR mutation might exist. We hypothesized that plasma microRNA (miRNA) might play a role. Methods: Training group: 20 advanced NSCLC patients treated with EGFR-TKIs as first-line therapy with EGFR 19 deletion mutation were enrolled, 10 of whom responded dramatically while other 10 are resistant. Matched plasma were collected for miRNA profile detection using TaqMan Low-Density (TLDA). Testing group: Real-time PCR were employed to identify the level of miRNAs found significant differently expressed in training step; bioinformatics was applied to find related miRNAs possibly account for resistance. Validation group: Another cohort with EGFR 19 deletion mutation present dramatically different response to EGFR-TKI was used to analyze the difference of miRNAs expression between responding and resistant group. Results: Training group: 153 miRNAs were found differently expressed between responding and resistant group. Testing group: 3 miRNAs (miR-21, AmiR-27a, and miR-218) were verified significantly higher (P=0.004, A0.009, A0.041, respectively) in resistant group than responding group. Validation group: expression level of these 3 miRNAs was validated to be significantly different (P=0.011, A0.011, A0.026, respectively) between 17 couples advanced NSCLC patients with different response to EGFR-TKI. Conclusions: Higher expression level of miR-21, AmiR-27a, and miR-218 might play the role in the resistance to EGFR-TKI for advanced NSCLC patients who had an EGFR exon 19 deletion mutation treated with EGFR-TKI, which needs further validation.

scholarly journals Efficacy and Acquired Resistance of EGFR-TKI Combined with Chemotherapy as First-Line Treatment for Chinese Patients with Advanced Non-Small Cell Lung Cancer in a Real-world Setting

2020 ◽  
Author(s):  
Qianqian Wang ◽  
Wen Gao ◽  
Fangyan Gao ◽  
Shidai Jin ◽  
Tianyu Qu ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Acquired Resistance ◽  
Small Cell ◽  
Combination Group ◽  
Monotherapy Group ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Nsclc Patients ◽  
Egfr Tki

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.

scholarly journals Combination of EGFR-TKIs with chemotherapy versus chemotherapy or EGFR-TKIs alone in advanced NSCLC patients with EGFR mutation

2018 ◽  
Vol Volume 12 ◽  
pp. 183-190 ◽  
Author(s):  
Miaomiao Wen ◽  
Jinghua Xia ◽  
Ying Sun ◽  
Xuejiao Wang ◽  
Xianghui Fu ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Nsclc Patients ◽  
Egfr Tkis

Changing causes of death post-epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) era in patients with advanced non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18132-e18132
Author(s):  
Wen Shuo Wu ◽  
Yuh-Min Chen ◽  
Chun-Ming Tsai ◽  
Jen-Fu Shih ◽  
Yu-Chin Lee ◽  
...  
Keyword(s):  
Causes Of Death ◽  
Hospice Care ◽  
Egfr Mutation ◽  
Kinase Inhibitor ◽  
Cns Metastases ◽  
Mutation Status ◽  
Tki Treatment ◽  
Nsclc Patients ◽  
Egfr Tki ◽  
Egfr Tkis

e18132 Background: EGFR-TKIs are effective against tumor EGFR-mutated NSCLC. Patients with tumor EGFR activating mutation (EGFRmu) (exon 19 deletions or exon 21 L958R) had better survival than those with EGFR wild-type tumors (EGFRwt). Many EGFRmu patients have had disease progression with EGFR-TKI treatment due to central nervous system (CNS) metastases, including meningeal carcinomatosis. The objective of this retrospective study is to compare the causes of death in patients with a known tumor EGFR mutation status who had been treated with EGFR-TKIs. Methods: We retrospectively reviewed the chart records of our advanced NSCLC patients who had received diagnosis, treatment, and supportive and hospice care in our hospital between July 2005 and June 2010. Tumor EGFR mutation status was analyzed using the DNA sequence method. All enrolled patients had a documented cause of death. Results: Ninety-four patients had documented tumor EGFR data, had received EGFR-TKI treatment (either erlotinib or gefitinib), and were with or without previous or salvage systemic chemotherapy. Of them, 36 were EGFRwt and 58 were EGFRmu. Overall survival after starting EGFR-TKI treatment was significantly longer in EGFRmu than in EGFRwt patients (median 68.9 weeks vs. 46.3 weeks, p=0.0058). Twenty-nine patients died of CNS metastases and 65 died of organ(s) failure other than the CNS. Patients who died of CNS metastases had undergone EKGF-TKI treatment significantly longer than those who died of other organ(s) failure (median 32 weeks vs. 7.7 weeks, p=0.0003), with a hazard ratio of 2.308 (95% C.I. 1.452-3.668, p=0.0004). A significantly higher proportion of EGFRmu patients died of CNS metastases (26 of 58, 44.8%) than EGFRwt patients (3 of 36, 8.3%) (p<0.001). Conclusions: EGFRmu NSCLC patients survived longer and had a significantly higher probability of mortality due to CNS metastases than EGFRwt patients. This change in the causes of death due to NSCLC was noted after an era of EGFR-TKI treatment, and will have an important impact on the strategies or management of patient supportive and hospice care.

Progression patterns at RECIST PD during EGFR-TKIs in advanced NSCLC patients harboring EGFR mutation.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8078-8078 ◽  
Author(s):  
Tatsuya Yoshida ◽  
Kiyotaka Yoh ◽  
Koichi Goto ◽  
Shingo Matsumoto ◽  
Shigeki Umemura ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Progression Free Survival ◽  
Initial Response ◽  
Cytotoxic Agents ◽  
Solitary Lesion ◽  
Multiple Lesions ◽  
Nsclc Patients ◽  
Egfr Tkis ◽  
Progression Patterns

8078 Background: The progression patterns at RECIST PD during EGFR-TKIs in advanced NSCLC patients harboring EGFR mutation are clinically heterogeneous. The aim of this study is to evaluate progression patterns at RECIST PD during EGFR-TKIs in advanced NSCLC patients harboring EGFR mutation. Methods: From 2008 to 2012, 160 consecutive patients with advanced NSCLC harboring EGFR mutation were treated with EGFR-TKIs (erlotinib or gefitinib) at our institution. Among these patients, 104 patients who experienced RECIST PD assessed by radiologic findings were retrospectively evaluated for initial response on EGFR-TKIs, progression sites, focus of progression (solitary lesion or multiple lesions), patients status at RECIST PD, and post progression survival (PPS) from RECIST PD. Results: In 104 patients, 96 (92%) patients had EGFR major mutation (Exon 19 deletion and L858R), and 49 (47%) received EGFR-TKIs as first-line. The overall response rate and median progression free survival on EGFR-TKIs was 69 % and 8.2 months. At the time of RECIST PD, 44 (42%) patients had symptomatic, and 60 (58%) had asymptomatic. The progression sites were isolated CNS in 17 (16%) patients, isolated bone in 7 (7%), isolated pulmonary in 13 (12%), systemic in 67 (65%) patients. In the focus of progression, 24 (23%) patients have solitary lesion, and 80 (77%) have multiple lesions. After RECIST PD, 40 (38%) patients continued EGFR-TKIs, 25 (24%) were switched to cytotoxic agents, and 39 (38%) had best supportive care. 10 (10%) patients received local radiotherapy for isolated progression site (brain 6; bone 3; lung 1) and 8 of these patients continued EGFR-TKIs. The median PPS from RECIST PD was 10.6 months. Multivariate analysis identified that asymptomatic or solitary progression lesion at RECIST PD were associated with significantly longer PPS (asymptomatic: HR 0.34, 95% CI 0.19-0.58, P<0.001; solitary progression lesion: HR 0.39, 95% CI 0.16-83, P=0.013). Conclusions: The progression patterns at RECIST PD during EGFR-TKIs in advanced NSCLC patients harboring EGFR mutation have widely diversity. Further investigation for association between progression patterns at RECIST PD and clinical outcome after RECIST PD is warranted.

Efficacy of EGFR-TKIs monotherapy versus TKI plus chemotherapy as first-line treatment in EGFR mutant lung adenocarcinoma with liver metastases.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21099-e21099
Author(s):  
Huijuan Wang ◽  
Mengmeng Li ◽  
Mina Zhang ◽  
Zhang guo Wei ◽  
Xiangtao Yan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Liver Metastases ◽  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Small Cell Lung ◽  
First Line ◽  
Chemotherapy Group ◽  
Nsclc Patients ◽  
Egfr Tkis

e21099 Background: Liver metastasis is one of the most reasons for the poor prognosis of patients with advanced lung cancer. Seeking for active and effective treatment measures is very important for these patients. At present, the first-line standard treatment of the advanced NSCLC with EGFR mutation is EGFR-TKIs monotherapy. However, its efficacy is poor in the advanced non-small cell lung cancer with EGFR mutation and liver metastases. The objective of this study is to evaluate the efficacy of EGFR-TKIs plus chemotherapy in patients with EGFR mutation of advanced non-small cell lung cancer with liver metastases. Methods: The clinical data of a total of 384 advanced NSCLC patients with EGFR mutation positive who were admitted to The Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital from February 2017 to June 2020 were retrospectively analyzed. There were 75 patients with liver metastases. Patients were divided into two groups, and accepted EGFR-TKIs monotherapy or EGFR-TKIs plus chemotherapy, respectively. All patients treatment response were evaluated by the RECIST1.1 Response evaluation criteria in solid tumors.Progression free-survival (PFS) were also analyzed. Results: In the study, 75 patients were finally screened. There were 37 patients in the EGFR-TKIs monotherapy group and 38 patients in the TKI plus chemotherapy group. The median follow-up time was 23.0 months. At the latest follow-up date (2021-01-01), 57 patients had disease progression and 35 patients had died. Comparing with EGFR-TKIs monotherapy,the first-line PFS of EGFR-TKI plus chemotherapy group was longer, and the median PFS was 12.7 months VS 7.4 months (P = 0.018).The ORR of primary lung lesions was no significant difference between these two groups（65.8%VS 51.4% P = 0.204), and DCR (97.4% VS 94.6% P = 0.981) also had no difference between two groups（P > 0.05）. ORR of liver metastases in the EGFR-TKIs plus chemotherapy group was significantly higher than EGFR-TKIs monotherapy group ORR (65.8%VS 40.5%，P = 0.028). Conclusions: In advanced NSCLC patients with EGFR mutation and liver metastases, comparing with EGFR-TKIs monotherapy, taking EGFR-TKIs plus chemotherapy as first-line treatment had longer PFS, and better efficacy on liver lesions.

scholarly journals Chinese Medicine Combined With EGFR-TKIs Prolongs Progression-Free Survival and Overall Survival of Non-small Cell Lung Cancer (NSCLC) Patients Harboring EGFR Mutations, Compared With the Use of TKIs Alone

2021 ◽  
Vol 9 ◽  
Author(s):  
Yujia Wang ◽  
Guoyu Wu ◽  
Ru Li ◽  
Yingzhe Luo ◽  
Xingmei Huang ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Progression Free Survival ◽  
Deletion Mutation ◽  
Control Group ◽  
Small Cell Lung ◽  
Free Survival ◽  
Exon 19 Deletion ◽  
Nsclc Patients ◽  
Experimental Group ◽  
Egfr Tkis

Objective: To explore the efficacy comparison between epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) combined with traditional Chinese medicine (TCM) and single EGFR-TKIs for advanced non-small cell lung cancer (NSCLC).Methods: A total of 91 NSCLC patients with EGFR mutation were divided into an experimental group and a control group (in a ratio of 2:1) to receive TCM and EGFR-TKIs (61 cases) or single EGFR-TKIs (30 cases). Patients in the control group took EGFR-TKIs and those in the experimental group took EGFR-TKIs plus TCM. We analyzed the progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and treatment-related adverse events of two groups.Results: The mPFS of the experimental group and the control group was 12.3 and 8.9 months (P = 0.02), respectively, and the mOS of the experimental group and the control group was 28.2 and 24.2 months (P = 0.02), respectively. Subgroup analysis showed that for the patients with exon 19 deletion mutation (19DEL), mPFS between experimental group and control group was 12.7 and 10.1 months, respectively (P = 0.12). For exon 21 deletion mutation (L858R), the PFS of two groups was 10.8 vs. 8.2 months, respectively (P = 0.03). The subgroup analysis also showed that, for the patients with exon 19 deletion mutation, mOS between the experimental group and the control group was 30.3 and 28.7 months, respectively (P = 0.19). For exon 21 deletion mutation, the mOS of two groups was 25.5 vs. 21.3 months, respectively (P = 0.01). The DCR of the experimental group and the control group was 93.3% and 80.1%, respectively (P = 0.77). Grade 3–4 treatment-related adverse events were less common with the experimental group (11.48%) than the control group (26.67%).Conclusion: For NSCLC patients with EGFR mutation, EGFR-TKIs combined with TCM had a certain effect to prolong mPFS and mOS, compared with the use of EGFR-TKIs alone, especially for the patients with L858R. This conclusion has a significant effect on improving the survival of NSCLC patients after EGFR-TKIs resistance. It deserves further study.

scholarly journals Use of the epidermal growth factor receptor inhibitors gefitinib, erlotinib, afatinib, dacomitinib, and icotinib in the treatment of non-small-cell lung cancer: a systematic review

2015 ◽  
Vol 22 (3) ◽  
pp. 183 ◽  
Author(s):  
P.M. Ellis ◽  
N. Coakley ◽  
R. Feld ◽  
S. Kuruvilla ◽  
Y.C. Ung
Keyword(s):  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Second Line ◽  
Small Cell Lung ◽  
First Line ◽  
Line Therapy ◽  
Epidermal Growth ◽  
Nsclc Patients ◽  
Egfr Tki ◽  
Egfr Tkis

Introduction This systematic review addresses the use of epidermal growth factor receptor (egfr) inhibitors in three populations of advanced non-small-cell lung cancer (nsclc) patients—unselected, selected, and molecularly selected—in three treatment settings: first line, second line, and maintenance.Methods Ninety-six randomized controlled trials found using the medline and embase databases form the basis of this review.Results In the first-line setting, data about the efficacy of egfr tyrosine kinase inhibitors (tkis) compared with platinum-based chemotherapy are inconsistent. Results from studies that selected patients based on clinical characteristics are also mixed. There is high-quality evidence that an egfr tki is preferred over a platinum doublet as initial therapy for patients with an activating mutation of the EGFR gene. The egfr tkis are associated with a higher likelihood of response, longer progression-free survival, and improved quality of life. Multiple trials of second-line therapy have compared an egfr tki with chemotherapy. Meta-analysis of those data demonstrates similar progression-free and overall survival. There is consequently no preferred sequence for second-line egfr tki or second-line chemotherapy. The egfr tkis have also been evaluated as switch-maintenance therapy. No molecular marker could identify patients in whom a survival benefit was not observed; however, the magnitude of the benefit was modest.Conclusions Determination of EGFR mutation status is essential to making appropriate treatment decisions in patients with nsclc. Patients who are EGFR mutation–positive should be treated with an egfr tki as first-line therapy. An egfr tki is still appropriate therapy in patients who are EGFR wild-type, but the selected agent should be administered as second- or third-line therapy.

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