9167 Outcomes with erlotinib in advanced NSCLC: examining the influence of increased EGFR gene copy number and EGFR mutations

2009 ◽  
Vol 7 (2) ◽  
pp. 556 ◽  
Author(s):  
D. Soulières ◽  
T. Ciuleanu ◽  
L. Stelmakh ◽  
R. Whittom ◽  
P. Delmar ◽  
...  
Keyword(s):  
Copy Number ◽  
Advanced Nsclc ◽  
Gene Copy Number ◽  
Egfr Mutations ◽  
Gene Copy ◽  
Egfr Gene

Correlation of the EGFR gene mutation, gene amplification and protein expression in non-small cell lung cancer with clinical outcomes of erlotinib monotherapy: An exploratory analysis of biomarkers by the Korean Cancer Study Group

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7608-7608
Author(s):  
M. Ahn ◽  
J. Ahn ◽  
S. Kim ◽  
H. Kim ◽  
J. Lee ◽  
...  
Keyword(s):  
Gene Amplification ◽  
Copy Number ◽  
Advanced Nsclc ◽  
Gene Copy Number ◽  
Egfr Mutations ◽  
Gene Copy ◽  
Egfr Gene ◽  
Cancer Study Group ◽  
Rate Of Response ◽  
Egfr Gene Mutation

7608 Background: Mutations in epidermal growth factor receptor (EGFR) are considered to be strong predictive marker for response to the EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients. The aim of this study conducted by the Korean Cancer Study Group (KCSG) was to determine the clinical implications of EGFR gene mutation, increased gene copy number or protein over- expression in Korean patients with advanced NSCLC who had been treated with erlotinib. Patients and Methods: A total of 120 patients received erlotinib at a dose of 150 mg daily as part of an open label phase II monotherapy trial between January 2005 and May 2006 in Korea. Ninety-two tissue samples obtained from these patients were analyzed for EGFR mutations (exon 18–21), 88 samples for EGFR gene amplification by real time PCR, and 77 samples for EGFR protein expression by immunohistochemical (IHC) staining. Results: Twenty-four out of 92 patients (26.1%) had EGFR mutations in exon 18, 19, or 21, most commonly in exon 19 (75%, 18/24). A higher frequencies were noted in female patients (40.0% vs 17.5%, p=0.017). Higher rate of response to erlotinib was noted in patients with EGFR mutations compared to wild type (N=14/24 (58.3%) vs 11/68 (16.2%), p<0.001). With the median follow-up duration of 14.5 months, time to progression (TTP) and overall survival (OS) were also significantly longer in patients with mutations than those without mutations (p=0.003, p=0.042). Increased EGFR gene copy number was found in 44.9% (36/88). Patients with increased gene copy number achieved higher rate of response to erlotinib (N=14/36 (38.9%) vs 9/52 (17.3%), p=0.023). Also patients with high gene copy number showed longer TTP and OS (p<0.001, p=0.022). Forty six out of 75 patients showed (+) IHC staining for EGFR protein although there was no relationship between the EGFR expression and the response to erlotinib, TTP or OS (p=0.82, p=0.35, p=0.83). Conclusion: EGFR mutation and gene amplification were shown to be important predictive markers not only for response but also for survival of the Korean patients with advanced NSCLC who had been treated with erlotinib. No significant financial relationships to disclose.

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.

Phase II pharmacodynamic trial of erlotinib in advanced non-small cell lung cancer (NSCLC) patients previously treated with platinum-based chemotherapy: FISH results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7160-7160 ◽  
Author(s):  
E. Felip ◽  
F. Rojo ◽  
M. Reck ◽  
A. Heller ◽  
B. Klughammer ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Copy Number ◽  
Advanced Nsclc ◽  
Gene Copy Number ◽  
Large Cell ◽  
Gene Copy ◽  
Egfr Gene ◽  
Previously Treated ◽  
Never Smokers ◽  
Nsclc Patients

7160 Background: The HER1/EGFR inhibitor erlotinib significantly prolongs survival of patients with previously-treated advanced NSCLC. Methods for selecting patients most likely to derive clinical benefit from erlotinib are not established. Increased HER1/EGFR gene copy number has been suggested as a potential predictive biomarker of clinical benefit, and was investigated in this phase II study. Methods: Advanced NSCLC patients who failed first line chemotherapy were treated with erlotinib monotherapy, 150 mg/d p.o. Each patient underwent tumor biopsy before start of treatment. Tumor HER1/EGFR gene amplification status was assessed using FISH, and classified as positive (amplification, polysomy, high polysomy) or negative (disomy, trisomy). Results: 83 patients were included: median age 56 (range 35–78); sex: male 72%, female 28%; histology: adenocarcinoma 43%, large cell 31%, squamous cell 19%, others 7%; smoking status: 44 current smokers, 28 former smokers, 11 never smokers. Of 73 evaluable patients, 7 (10%) achieved partial response (PR), 28 (38%) had stable disease (SD) and 38 (52%) had disease progression. PRs were observed in 4 males / 3 females; in 5 adenocarcinomas / 1 large cell/ 1 squamous cell; in 2 current / 3 former / 2 never smokers. Erlotinib was well tolerated and no unexpected toxicities were seen. HER1/EGFR gene copy number was evaluated in 53 patients. 15 patients were FISH +, 10 of whom achieved clinical benefit (PR, or SD for ≥12 weeks). Only 5 of 38 FISH - patients had clinical benefit. FISH + patients achieved a longer median time to progression (137 vs 43 days; p = 0.00011; HR 0.35) as well as overall survival (226 vs 115 days; p = 0.3221, HR 0.722). Conclusion: In this study, increased HER1/EGFR gene copy number was associated with a better outcome on erlotinib therapy. [Table: see text] [Table: see text]

Molecular Predictors of Outcome With Gefitinib in a Phase III Placebo-Controlled Study in Advanced Non–Small-Cell Lung Cancer

2006 ◽  
Vol 24 (31) ◽  
pp. 5034-5042 ◽  
Author(s):  
Fred R. Hirsch ◽  
Marileila Varella-Garcia ◽  
Paul A. Bunn ◽  
Wilbur A. Franklin ◽  
Rafal Dziadziuszko ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Protein Expression ◽  
Copy Number ◽  
Gene Copy Number ◽  
Phase Iii ◽  
Egfr Mutations ◽  
Gene Copy ◽  
Egfr Gene ◽  
Low Copy Number ◽  
Gefitinib Treatment

Purpose The phase III Iressa Survival Evaluation in Lung Cancer (ISEL) trial compared gefitinib with placebo in 1,692 patients with refractory advanced non–small-cell lung cancer. We analyzed ISEL tumor biopsy samples to examine relationships between biomarkers and clinical outcome after gefitinib treatment in a placebo-controlled setting. Methods Biomarkers included epidermal growth factor receptor (EGFR) gene copy number by fluorescence in situ hybridization (n = 370); EGFR (n = 379) and phosphorylated Akt (p-Akt) protein expression (n = 382) by immunohistochemistry; and mutations in EGFR (n = 215), KRAS (n = 152), and BRAF (n = 118). Results High EGFR gene copy number was a predictor of a gefitinib-related effect on survival (hazard ratio [HR], 0.61 for high copy number and HR, 1.16 for low copy number; comparison of high v low copy number HR, P = .045). EGFR protein expression was also related to clinical outcome (HR for positive, 0.77; HR for negative, 1.57; comparison of high v low protein expression HR, P = .049). Patients with EGFR mutations had higher response rates than patients without EGFR mutations (37.5% v 2.6%); there were insufficient data for survival analysis. No relationship was observed between p-Akt protein expression and survival outcome, and the limited amount of data collected for KRAS and BRAF mutations prevented any meaningful evaluation of clinical outcomes in relation to these mutations. Conclusion EGFR gene copy number was a predictor of clinical benefit from gefitinib in ISEL. Additional studies are warranted to assess these biomarkers fully for the identification of patients most likely to benefit from gefitinib treatment.

Abstract 2396: High EGFR gene copy number predicts poor outcome in triple-negative breast cancer.

2013 ◽  
Author(s):  
Heae Surng Park ◽  
Min Hye Jang ◽  
Eun Joo Kim ◽  
Hyun Jeong Kim ◽  
Hee Jin Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Copy Number ◽  
Triple Negative ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Egfr Gene ◽  
Poor Outcome
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