Phase II study of gefitinib for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) gene mutations detected by PNA-LNA PCR clamp

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7076-7076 ◽  
Author(s):  
A. Sutani ◽  
Y. Nagai ◽  
K. Udagawa ◽  
Y. Uchida ◽  
Y. Murayama ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Response Rate ◽  
Phase Ii Study ◽  
Gene Mutations ◽  
Egfr Mutations ◽  
Wild Type ◽  
First Line ◽  
Egfr Gene ◽  
Nsclc Patients ◽  
Egfr Genes

7076 Background: The responsiveness to gefitinib has been reported to closely link to the presence of EGFR gene mutations. We developed a method, PNA-LNA PCR clamp, capable of detecting EGFR mutations in the presence of 100-fold background of wild type EGFR from normal cells (Can Res. 2005;65:7276). This study was prospectively designed to evaluate 1) the sensitivity and the specificity of the PNA-LNA PCR clamp (sample size > 100 pts) and 2) a phase II study of gefitinib for NSCLC patients (pts) with EGFR gene mutations (sample size > 25 pts to show the lower limit of 95% CI > 50%). Methods: Clinical samples (sputum, pleural effusion, bronchial fluid and paraffin tissue) were obtained from consecutive NSCLC pts with informed consent in our institution, and were tested by the PNA-LNA PCR clamp. After the second informed consent, for PS 0–2, inoperable stage III and IV pts with EGFR mutations, gefitinib (250mg P.O. daily) was given as the second treatment after docetaxel containing chemotherapy. In case of poor PS pts, the first line chemotherapy was omitted. Results: From Sept. ’04 to Oct. ’05, samples from 100 of a total of 107 pts were informative of EGFR mutation status. PNA-LNA PCR clamp detected EGFR mutations in 38 pts (38%) (15 males/23 females; median age:62; adenoca.:33 pts). Exon 19 deletions, L858R and L861Q were found in 25 (66%), 12 (32%) and 1 (2%) patients, respectively. But 62 pts (51 males/11 females; median age:66; Ad:43 pts) were judged to have wild type EGFR. Between positive and negative pts in EGFR mutation, there was significant difference in the distinction of sex (p = 0.00001). Gefitinib was given to 26 pts with EGFR mutations as the first line (4 pts) or the second line treatment (22 pts). One patient and 20 patients showed CR and PRs, respectively, and the response rate was 81% (95% CI: 61–94%). For patients with wild EGFR genes, gefitinib was given to 5 patients and one patient (20%) showed PR. The response rate was significantly different between wild and mutant EGFR genes detected by the PNA-LNA PCR clamp (p = 0.017). Conclusions: PNA-LNA PCR clamp could reliably detect EGFR mutations, indicating the method is useful to detect EGFR mutations in clinical specimens. Updated data will be presented at the meeting. No significant financial relationships to disclose.

A phase II study of gefitinib as a first-line therapy for advanced non-small cell lung cancers with epidermal growth factor receptor (EGFR) gene mutations

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13014-13014 ◽  
Author(s):  
H. Asahina ◽  
K. Yamazaki ◽  
I. Kinoshita ◽  
S. Ogura ◽  
T. Ishida ◽  
...  
Keyword(s):  
Phase Ii Study ◽  
Growth Factor Receptor ◽  
Gene Mutations ◽  
Small Cell Lung ◽  
First Line ◽  
Lung Cancers ◽  
Egfr Gene ◽  
First Line Therapy ◽  
Line Therapy ◽  
Epidermal Growth

13014 Background: Activating mutations in exon 18–21 of the epidermal growth factor receptor (EGFR) gene have been reported to be a predictor of response to gefitinib. We conducted a phase II study to evaluate the efficacy and safety of gefitinib as a first-line therapy for advanced non-small cell lung cancers (NSCLCs) with EGFR gene mutations. Methods: The primary endpoint was response rate (RR). Eligiblity criteria were stage IIIB or IV chemotherapy naive NSCLC, ECOG PS of 0–2, adequate organ functions, measurable lesions, and written informed consent. First, we examined EGFR gene mutations in exon 18–21 by direct sequencing of PCR products of DNA extracted from paraffin-embedded tissues. Those who had EGFR gene mutations received gefitinib 250 mg daily. This study, with a sample size of 14, had 90% power to support the hypothesis that true RR was ≥70%, and 5% significance to deny the hypothesis that true RR was ≤30%. Assuming an inevaluality rate ≤15%, we projected an accrual of 16 patients. Results: From Nov. 2004 to Jan. 2006, EGFR gene mutations were analyzed in tumor specimens from 82 patients. Twenty patients (24%) had EGFR gene mutations (16 with deletions in or near E746-A750, 4 with L858R). While there were no significant differences between mutation status and age, sex, histology, or the procedures to obtain tumor specimens, EGFR gene mutations were more frequently observed in never-smokers than in smokers (39% vs. 11%, p<0.01). Sixteen patients (median age, 68; male/female, 3/13; adenocarcinoma/SCC, 15/1; current/former/never smoker, 2/1/13) were enrolled and treated with gefitinib. To date, best response is 2 CR, 7 PR, 1 SD and 1 PD (RR, 82%). Two patients had grade 3 toxicities, including 1 skin eruption and 1 liver dysfunction. One patient had grade 1 interstitial lung disease, leading to the termination of gefitinib treatment. Conclusions: Gefitinib is very active and well tolerated as a first-line therapy for advanced NSCLCs with EGFR gene mutations. No significant financial relationships to disclose.

Multicenter phase II study of FOLFOX or biweekly XELOX and cetuximab as first-line treatment in patients with wild-type KRAS/BRAF metastatic colorectal cancer (mCRC) (FLEET study).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 463-463
Author(s):  
Ho Min Kim ◽  
Hitoshi Soda ◽  
Shoichi Hazama ◽  
Takao Takahashi ◽  
Naoki Nagata ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Predictive Biomarker ◽  
Wild Type ◽  
First Line ◽  
First Line Therapy ◽  
Multicenter Phase ◽  
Grade 3 ◽  
Few Data

463 Background: Cetuximab and chemotherapy as first-line therapy for patients with KRAS wild type prolong survival. However, COIN trial has not demonstrated the survival benefit of FOLFOX or XELOX and cetuximab therapy. Few data are available on its benefit for patients with KRAS and BRAF wild-type. Methods: The aim of this study was to assess the efficacy of first-line FOLFOX or bi-weekly XELOX and bi-weekly cetuximab in KRAS/BRAF wt mCRC. Chemonaive patients received FOLFOX or biweekly XELOX (oxaliplatin 85 mg/ m2/day 1 plus capecitabine 2000/m2/days 1-7) and biweekly cetuximab 500mg m2/ day 1 every 2 weeks. Primary endpoint was response rate(RR), other secondary endpoints were PFS, OS, DCR, safety, DI and resection rate. KRAS test (codon12,13) and BRAF test (V600E) by direct sequence were performed in Yamaguchi University. Patients with KRAS/BRAF wt were enrolled in this study. The regimen of FOLFOX or XELOX were selected by investigator’s preference, not randomized. Results: From April 2010 to May 2011, 139 pts were preregistered. KRAS and BRAF were examined from paraffin-embedded sample. 70 (50.3%) pts were KRAS/BRAF wt, and 62 pts were enrolled: The main characteristics of the entered pts were: sex (M/F) 34/28, median age 66 yrs (range 34-83 yrs). Grade 3/4 adverse events were leucopenia 4.8%, neutropenia 25.8%, skin toxity (paronychia/fissure) 9.7%, and acne 9.7%. Two CR (3.2%) and 40 PR (64.5%), 15 SD (24.2%) and 3 PD (4.8%) 2NE were observed, with an overall response rate of 67.7% and a disease control rate (CR+PR+SD) of 91.9%. The RR of FOLFOX or XELOX were 64.9% (24/37) and 72.0% (18/25), DCR were 89.2% and 96% respectively. Conclusions: FLEET was the first multicenter phase II study with prospective KRAS/BRAF analysis as a predictive biomarker for cetuximab in first-line mCRC in Japan. Results of this study indicate that both biweekly combination regimens are feasible, tolerable, and clinically active. Biweekly XELOX+cetuximab study (FLEET2) is ongoing. Clinical trial information: UMIN000003253.

A Phase II study to evaluate the efficacy of erlotinib in advanced NSCLC patients who have wild-type EGFR and EGFR gene amplification.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e19028-e19028
Author(s):  
Takashi Sone ◽  
Tomoyuki Araya ◽  
Yuichi Tambo ◽  
Kazuhiko Shibata ◽  
Shingo Nishikawa ◽  
...  
Keyword(s):  
Gene Amplification ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Phase Ii Study ◽  
Wild Type ◽  
Egfr Gene ◽  
Nsclc Patients

Exploring the applicability of immunotherapy in different EGFR mutation subgroups based on data analysis of 9,659 Chinese patients with NSCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21020-e21020
Author(s):  
Hao Peng ◽  
Hushan Zhang ◽  
Libin Zhang ◽  
Yang Wang ◽  
Xudong Shen ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Egfr Mutation ◽  
Clinical Laboratory ◽  
Checkpoint Inhibitors ◽  
White Blood Cells ◽  
Chinese Patients ◽  
Egfr Mutations ◽  
Wild Type ◽  
Tissue Samples ◽  
Nsclc Patients

e21020 Background: Here we assessed TMB level, PD-L1 expression, and their correlation in 9649 Chinese NSCLC patients with or without EGFR mutation, and different subtypes of EGFR mutations, to find out the underlying mechanisms that different outcomes of ICI for EGFR wild type and EGFR mutation NSCLC patients, and the possibility of ICI therapy for NSCLC patients of different EGFR mutation subtypes. Methods: Tumor tissue samples of 9649 NSCLC patients were collected from Janary 2018, expression of PD-L1 were detected by using Dako PD-L1 IHC 22C3 pharmDx, Tumor Proportion Score (TPS) was used to determine expression of PD-L1. Gene mutation was detected by means of next generation sequencing (NGS). Performed Whole-Exome Sequencing (WES) on 70 tissue samples and corresponding White Blood Cells (WBCs) as matched control. Other samples were detected with panel covering whole exon regions of 733 cancer related genes. All these detections were performed in a College of American Pathologists (CAP)-certified and Clinical Laboratory Improvement Amendments (CLIA)-accredited lab for gene mutation analysis (3D Medicines Inc.,Shanghai, China). Statistical analysis was performed using GraphPad Prism (version 7.01) and SPSS version 21.0 (SPSS,Inc.). Results: Results showed that the proportion of EGFR mutation in Chinese patients with NSCLC was 51.3%, and the proportion of EGFR mutation subtypes were 42.6% L858R, 39.5% exon 19del, 2.3% exon 20in, 4.3% T790M. These samples were divided into different groups according to EGFR mutation, both WES based and panel-based results showed that EGFR wild type group displayed higher TMB level than EGFR mutation group (P < 0.05). However, except for exon 19del, L858R, exon 20in, no significant differences were found between wild type and other EGFR mutation subtypes. Furthermore, results of IHC revealed that, higher proportion of strong positive PD-L1 expression (TPS≥50) were found in EGFR wild type than exon 19del, L858R and exon 20in, no significant correlation was found between TMB level and PD-L1 expression. Conclusions: EGFR mutations account for half of Chinese NSCLC patients. The biomarkers of immune checkpoint inhibitors (such as TMB and PD-L1) are different in various EGFR mutation subtypes, which may indicate that for some NSCLC patients with EGFR mutation subtypes, they may also respond to ICI treatment as wild-type.

Biomarker Analyses and Final Overall Survival Results From a Phase III, Randomized, Open-Label, First-Line Study of Gefitinib Versus Carboplatin/Paclitaxel in Clinically Selected Patients With Advanced Non–Small-Cell Lung Cancer in Asia (IPASS)

2011 ◽  
Vol 29 (21) ◽  
pp. 2866-2874 ◽  
Author(s):  
Masahiro Fukuoka ◽  
Yi-Long Wu ◽  
Sumitra Thongprasert ◽  
Patrapim Sunpaweravong ◽  
Swan-Swan Leong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Copy Number ◽  
Egfr Mutation ◽  
Gene Copy Number ◽  
Phase Iii ◽  
Egfr Mutations ◽  
Gene Copy ◽  
First Line ◽  
Egfr Gene ◽  
Significant Difference

Purpose The results of the Iressa Pan-Asia Study (IPASS), which compared gefitinib and carboplatin/paclitaxel in previously untreated never-smokers and light ex-smokers with advanced pulmonary adenocarcinoma were published previously. This report presents overall survival (OS) and efficacy according to epidermal growth factor receptor (EGFR) biomarker status. Patients and Methods In all, 1,217 patients were randomly assigned. Biomarkers analyzed were EGFR mutation (amplification mutation refractory system; 437 patients evaluable), EGFR gene copy number (fluorescent in situ hybridization; 406 patients evaluable), and EGFR protein expression (immunohistochemistry; 365 patients evaluable). OS analysis was performed at 78% maturity. A Cox proportional hazards model was used to assess biomarker status by randomly assigned treatment interactions for progression-free survival (PFS) and OS. Results OS (954 deaths) was similar for gefitinib and carboplatin/paclitaxel with no significant difference between treatments overall (hazard ratio [HR], 0.90; 95% CI, 0.79 to 1.02; P = .109) or in EGFR mutation–positive (HR, 1.00; 95% CI, 0.76 to 1.33; P = .990) or EGFR mutation–negative (HR, 1.18; 95% CI, 0.86 to 1.63; P = .309; treatment by EGFR mutation interaction P = .480) subgroups. A high proportion (64.3%) of EGFR mutation–positive patients randomly assigned to carboplatin/paclitaxel received subsequent EGFR tyrosine kinase inhibitors. PFS was significantly longer with gefitinib for patients whose tumors had both high EGFR gene copy number and EGFR mutation (HR, 0.48; 95% CI, 0.34 to 0.67) but significantly shorter when high EGFR gene copy number was not accompanied by EGFR mutation (HR, 3.85; 95% CI, 2.09 to 7.09). Conclusion EGFR mutations are the strongest predictive biomarker for PFS and tumor response to first-line gefitinib versus carboplatin/paclitaxel. The predictive value of EGFR gene copy number was driven by coexisting EGFR mutation (post hoc analysis). Treatment-related differences observed for PFS in the EGFR mutation–positive subgroup were not apparent for OS. OS results were likely confounded by the high proportion of patients crossing over to the alternative treatment.

Prospective analysis of the epidermal growth factor receptor gene mutations in non-small cell lung cancer in Japan

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7077-7077 ◽  
Author(s):  
N. Morikawa ◽  
A. Inoue ◽  
T. Suzuki ◽  
T. Fukuhara ◽  
S. Suzuki ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Egfr Mutation ◽  
Response Rate ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Epidermal Growth ◽  
Nsclc Patients

7077 Background: Previous clinical trials have revealed that gefitinib is more likely to be effective in non-small cell lung cancer (NSCLC) with activating somatic mutations of epidermal growth factor receptor (EGFR). Most of those reports evaluated NSCLC patients who had post-operative recurrence and then received gefitinib retrospectively using their surgical specimens. However, many NSCLC patients are inoperable at diagnosis. Thus we conducted this study to examine EGFR mutation status by diagnostic tumor samples before gefitinib treatment and investigate the correlation between EGFR mutation and the efficacy of gefitinib. Methods: We prospectively evaluated various tumor samples obtained from NSCLC patients who had never received gefitinib for EGFR mutations in exon 18–23. For patients treated with gefitinib after the examination of EGFR mutations, the response to gefitinib was also evaluated. Results: From June 2004 to November 2005, 91 patients with advanced or post-operative recurrent NSCLC enrolled onto this study and 104 tumor samples were obtained from transbronchial biopsies, effusions, as well as surgical specimens. Thirty-two mutations including deletions in exon 19 in 23 patients and L858R in 9 patients were detected among those 91 patients; 30 in 81 adenocaricinoma, 1 in 2 adenosquamous cell carcinoma, and 1 in 5 large cell carcinoma. The mutations were found more frequently in female (51.9%) than male (12.8%), in never smoker (52.0%) than smoker (14.6%). Response rate of gefitinib in patients with EGFR mutations was 65.0% (13 of 20) compared to 37.5% (3 of 8) in patients without mutations. Among 7 patients with EGFR mutations who were examined multiple tumor samples, 3 had the discrepancy of EGFR gene status between different samples obtained at different time points, suggesting genetic heterogeneity of their tumors. The EGFR status of the most recent samples is likely to be correlated to the response to gefitinib. Conclusions: The EGFR mutation analysis was possible not only from surgical specimens but also from daily available diagnostic samples. For patients with EGFR mutations, gefitinib could achieve a promising high response rate. We propose to examine the most recent tumor samples to predict the sensitivity to gefitinib reliably. No significant financial relationships to disclose.

Association of plasma EGFR mutations with response to first-line chemotherapy and prognosis in Chinese patients with advanced non-small cell lung cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19017-e19017
Author(s):  
M. N. Wu ◽  
J. Zhao ◽  
H. Bai ◽  
M. L. Zhuo ◽  
S. H. Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stage Iv ◽  
Small Cell ◽  
Chinese Patients ◽  
Egfr Mutations ◽  
Wild Type ◽  
Small Cell Lung ◽  
First Line ◽  
Nsclc Patients ◽  
Line Chemotherapy

e19017 Background: To investigate associations of plasma EGFR mutations of advanced non-small cell lung cancer (NSCLC) patients with response to the first-line chemotherapy and prognosis. Methods: Plasma EGFR mutations from 145 chemotherapy-naive patients with advanced or metastatic NSCLC were examined by using denaturing high- performance liquid chromatography (DHPLC), and associations of EGFR mutations with tumor response to chemotherapy and clinical outcomes were evaluated. Results: 37.2% (54/145) of the patients was detected to have EGFR mutations in their plasma DNA. The response rate of mutated EGFR carriers to the chemotherapy was 37% (20/54), similar to that of 31.9% (29/91) of wild-type EGFR carriers to the chemotherapy (P= 0.323). Stage IV NSCLC patients with mutated EGFR had a longer PFS than those with wild-type EGFR (4 vs 3 months, P=0.043) after the first-line chemotherapy. The median survival time and 1-, 2- year survival rate for the patients with EGFR mutations (24 months and 85.7%,43.7%) were increased than those with wild-type EGFR (18 months and 65.7%,25.9%) (p=0.0468). Cox multivariate regression analysis showed that clinical stage (IV vs IIIb), response to the first-line chemotherapy (PR vs PD), and EGFR mutations were independent prognostic factors (P=0.008, 0.000 and 0.000 respectively). Conclusions: We conclude that plasma EGFR mutations in the Chinese patients with advanced NSCLC were not associated with response to the first-line chemotherapy, but Stage IV NSCLC patients with mutated EGFR had a longer PFS after the chemotherapy. No significant financial relationships to disclose.

scholarly journals A Phase II Study of Erlotinib as First-Line Treatment in Japanese Advanced NSCLC Patients Harboring EGFR Mutations

2012 ◽  
Vol 23 ◽  
pp. ix413 ◽  
Author(s):  
A. Horiike ◽  
M. Nishio ◽  
K. Goto ◽  
N. Yamamoto ◽  
K. Chikamori ◽  
...  
Keyword(s):  
Phase Ii ◽  
Advanced Nsclc ◽  
Phase Ii Study ◽  
Egfr Mutations ◽  
Line Treatment ◽  
First Line ◽  
Nsclc Patients ◽  
First Line Treatment

SpecificEGFRMutations Predict Treatment Outcome of Stage IIIB/IV Patients With Chemotherapy-Naive Non–Small-Cell Lung Cancer Receiving First-Line Gefitinib Monotherapy

2008 ◽  
Vol 26 (16) ◽  
pp. 2745-2753 ◽  
Author(s):  
Chih-Hsin Yang ◽  
Chong-Jen Yu ◽  
Jin-Yuan Shih ◽  
Yeun-Chung Chang ◽  
Fu-Chang Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Multivariate Analysis ◽  
Response Rate ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
First Line ◽  
Exon 19 Deletion ◽  
Nsclc Patients ◽  
Exon 19

PurposeTo explore predictive factors for time to treatment failure (TTF) in chemotherapy-naive non–small-cell lung cancer (NSCLC) patients receiving gefitinib treatment.Patients and MethodsWe designed a phase II study to test gefitinib antitumor efficacy in advanced-stage, chemotherapy-naive NSCLC patients. Patients were treated with gefitinib 250 mg/d. Tumor assessments were performed every 2 months. Responding or stable patients were treated until progression or unacceptable toxicity. All scans were reviewed independently. EGFR exons 18-21 sequence, K-ras exon 2 sequence, and MET gene copy numbers were examined in available samples. Clinical or molecular predictors of TTF were examined by multivariate analysis.ResultsOne hundred six patients were enrolled. Ninety patients had tumor samples for biomarker tests. Overall response rate was 50.9% (95% CI, 41.4% to 60.4%). Median TTF was 5.5 months, and median overall survival (OS) was 22.4 months. The response rate and median TTF of the patients with exon 19 deletion (n = 20) were 95.0% and 8.9 months, for exon 21 L858R mutation (n = 23) were 73.9% and 9.1 month, and for other types of EGFR mutations (N = 12) were 16.7% and 2.3 months, respectively. In multivariate analysis, the presence of EGFR deletion exon 19 or L858R EGFR mutations in adenocarcinoma patients predicted longer TTF. High copy number of MET seemed to correlate with shorter TTF in patients with gefitinib-sensitive activating EGFR mutations.ConclusionIn this prospective study, EGFR exon 19 deletion or L858R mutations in adenocarcinoma were the best predictors for longer TTF in stage IIIB/IV chemotherapy-naive NSCLC patients receiving first-line gefitinib monotherapy.

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