scholarly journals Evaluation of EGFR gene copy number as a predictive biomarker for the efficacy of cetuximab in combination with chemotherapy in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck: EXTREME study

2011 ◽  
Vol 22 (5) ◽  
pp. 1078-1087 ◽  
Author(s):  
L. Licitra ◽  
R. Mesia ◽  
F. Rivera ◽  
É. Remenár ◽  
R. Hitt ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Copy Number ◽  
Gene Copy Number ◽  
Predictive Biomarker ◽  
Gene Copy ◽  
Line Treatment ◽  
First Line ◽  
Egfr Gene ◽  
Metastatic Squamous Cell Carcinoma ◽  
First Line Treatment

Biomarker potential of EGFR gene copy number by FISH in the phase III EXTREME study: Platinum-based CT plus cetuximab in first-line R/M SCCHN

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6005-6005 ◽  
Author(s):  
L. Licitra ◽  
F. Rolland ◽  
C. Bokemeyer ◽  
E. Remenar ◽  
H. Kienzer ◽  
...  
Keyword(s):  
Copy Number ◽  
Gene Copy Number ◽  
Predictive Biomarker ◽  
Fish Population ◽  
Phase Iii ◽  
Gene Copy ◽  
First Line ◽  
Egfr Gene ◽  
Evaluable Population ◽  
Fish Cells

6005 Background: Platinum-based CT + cetuximab is the first systemic therapy in ∼30 years to show a survival benefit vs platinum-based CT in first-line R/M SCCHN (Vermorken JB, et al. N Engl J Med 2008;359:1116–1127). A retrospective analysis has evaluated the influence of EGFR gene copy number, determined by FISH, on clinical outcome in the EXTREME study. Methods: Pts were randomized to 3-weekly cycles of platinum-based CT (cisplatin 100 mg/m2 or carboplatin AUC 5, day 1; 5-fluorouracil 1000 mg/m2/day continuous infusion, days 1–4) with or without cetuximab (initial dose 400 mg/m2, then 250 mg/m2 weekly). The proportion of FISH+ cells per pt (FISH score) was determined using 5 different enrichment models. Tumors were also classified as FISH+ or FISH- using the Colorado scoring system. Results: In the overall population (n=442), addition of cetuximab significantly improved median OS (10.1 vs 7.4 months; p=0.04). No association between FISH score and OS, PFS, or best overall response was determined for any enrichment model. Pts with Colorado FISH+ tumors were evenly distributed between the CT + cetuximab (50/158) and CT-alone (51/154) arms of the FISH- evaluable population (71% of ITT population). Colorado FISH status had no influence on OS in either treatment arm, on PFS in the CT-alone arm, or on RR in the CT + cetuximab arm (see table ). In the CT + cetuximab arm, pts with FISH+ tumors had a lower risk of progression than pts with FISH- tumors. Higher RRs among pts with FISH- tumors in the CT-alone arm may have been due to twice as many nonevaluable response observations in the FISH+ vs the FISH- population (percentage of pts with SD or PD was comparable). Conclusions: EGFR gene copy number, as determined by FISH, is not a predictive biomarker for cetuximab efficacy in R/M SCCHN. [Table: see text] [Table: see text]

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.

scholarly journals EGFR gene copy number as a predictive biomarker for the treatment of metastatic colorectal cancer with anti-EGFR monoclonal antibodies: a meta-analysis

2012 ◽  
Vol 5 (1) ◽  
pp. 52 ◽  
Author(s):  
Zu-Yao Yang ◽  
Wei-Xi Shen ◽  
Xue-Feng Hu ◽  
Da-Yong Zheng ◽  
Xin-Yin Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Monoclonal Antibodies ◽  
Metastatic Colorectal Cancer ◽  
Copy Number ◽  
Meta Analysis ◽  
Gene Copy Number ◽  
Predictive Biomarker ◽  
Gene Copy ◽  
Egfr Gene
Sign in / Sign up

Export Citation Format

Share Document