scholarly journals Epidermal Growth Factor Receptor Mutation Status and Adjuvant Chemotherapy With Uracil-Tegafur for Adenocarcinoma of the Lung

2007 ◽  
Vol 25 (25) ◽  
pp. 3952-3957 ◽  
Author(s):  
Hiroshi Suehisa ◽  
Shinichi Toyooka ◽  
Katsuyuki Hotta ◽  
Akiko Uchida ◽  
Junichi Soh ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Adjuvant Chemotherapy ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Wild Type ◽  
Mutation Status ◽  
Epidermal Growth ◽  
Egfr Mutant ◽  
Lung Adenocarcinomas ◽  
Mutant Cells

Purpose Adjuvant chemotherapy with uracil-tegafur has been demonstrated to prolong survival among patients with resected lung adenocarcinomas. Epidermal growth factor receptor (EGFR) mutations have been reported to be present in lung adenocarcinomas. The present study evaluated whether the EGFR status could be used as a biologic predictor of the outcome of adjuvant chemotherapy with uracil-tegafur. Patients and Methods The EGFR mutational status of 187 patients with resected lung adenocarcinomas was determined using a polymerase chain reaction–based assay for EGFR exons 19 and 21; the results were then correlated with the effect of adjuvant uracil-tegafur chemotherapy on survival. The antiproliferative effect of fluorouracil (FU) on adenocarcinoma cell lines with EGFR wild-type or mutant type status was examined by measuring the inhibitory concentrations at 50% (IC50s). Results Among the 187 patients, 68 received uracil-tegafur as adjuvant chemotherapy, and 119 were not treated with any chemotherapeutic agents. EGFR mutations were present in 79 patients (43%). Overall, the adjuvant chemotherapy with uracil-tegafur significantly prolonged survival compared with the control group (hazard ratio = 0.38; P = .005). The survival benefit of adjuvant chemotherapy with uracil-tegafur was also examined after stratifying the patients according to EGFR mutation status. Adjuvant chemotherapy significantly prolonged survival among patients with EGFR wild-type tumors (hazard ratio = 0.34; P = .013) but not among patients with EGFR mutant tumors. In an in vitro experiment, the IC50s of EGFR mutant cells to FU were higher than those of wild-type cells, indicating that EGFR wild-type cells are more sensitive to FU than mutant cells. Conclusion EGFR status influenced the effect of adjuvant chemotherapy with uracil-tegafur. Adjuvant chemotherapy could be customized based on EGFR status.

Epidermal growth factor receptor mutation status and adjuvant chemotherapy in resected advanced non-small cell lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7034-7034 ◽  
Author(s):  
Si-Yu Wang ◽  
Haibo Sun ◽  
Wei Ou ◽  
Qin Fang
Keyword(s):  
Overall Survival ◽  
Epidermal Growth Factor Receptor ◽  
Adjuvant Chemotherapy ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Egfr Mutations ◽  
Wild Type ◽  
Free Survival ◽  
Epidermal Growth ◽  
Disease Free

7034 Background: Mutations in the epidermal growth factor receptor (EGFR) are associated with response to chemotherapy in patients with advance NSCLC. The purpose of this study was to assess the association of mutations in the EGFR tyrosine kinase domain and the efficacy of adjuvant chemotherapy in patients with fully resected IIIA-N2 NSCLC tumors. Methods: Tumor samples (n =150) from patients in our prior trial with IIIA-N2 NSCLC who either had or had not received paclitaxel/vinorelbine plus carboplatin chemotherapy following removal of the tumor were analyzed for EGFR mutations in exons 19 and 21. The association of the presence of EGFR mutations and survival following treatment was assessed. Results: Mutations were identified in 33 (22%) patients (n=13 in the no chemotherapy [observation] arm and n=20 in the chemotherapy arm). Fourteen patients (9.3%) had deletion mutations in exon 19, and 19 patients (12.7%) had a substitution mutation in exon 21. Compared with patients wild-type for EGFR, patients with EGFR mutations had numerical but not statistically significant improved disease-free survival (35 months [95% CI, 14.6-55.4] versus 23 months [95% CI, 17.3-28.7], respectively, P=0.339) and overall survival (36 months [95% CI, 27.9 to 44.1] versus 26 months [95% CI, 20.1 to 31.9], respectively p=0.271) regardless of treatment. Patients with wild-type EGFR had greater overall survival with chemotherapy compared to no adjuvant therapy (HR=1.920; 95%CI, 1.245-2.963; p=0.003). In contrast, EGFR mutant patients in the observation group compared to the chemotherapy group had longer median disease-free survival (35 months [95% CI, 20.9 to 49.1] versus 27 months [95% CI, 5.3 to 48.7], respectively, p=0.671) and overall survival (33 months [95% CI, 24.2 to 41.8] versus 40 months [95% CI, 31.8 to 48.2] respectively, p =0.360). Conclusions: In this study, the status of mutations in exons 19 and 21 of EGFR was associated with different clinical outcomes in patients with resected IIIA-N2 NSCLC tumors either treated with or without adjuvant chemotherapy. These findings suggest that a patient’s treatment should be customized to their EGFR mutational status.

Use of Cigarette-Smoking History to Estimate the Likelihood of Mutations in Epidermal Growth Factor Receptor Gene Exons 19 and 21 in Lung Adenocarcinomas

2006 ◽  
Vol 24 (11) ◽  
pp. 1700-1704 ◽  
Author(s):  
DuyKhanh Pham ◽  
Mark G. Kris ◽  
Gregory J. Riely ◽  
Inderpal S. Sarkaria ◽  
Tiffani McDonough ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Receptor Gene ◽  
Growth Factor Receptor ◽  
Smoking History ◽  
Egfr Mutations ◽  
Epidermal Growth ◽  
Former Smokers ◽  
Never Smokers ◽  
Lung Adenocarcinomas ◽  
Exon 19

Purpose Lung adenocarcinomas with mutations in exons 19 and 21 of the epidermal growth factor receptor gene (EGFR) demonstrate sensitivity to gefitinib or erlotinib. Investigators have reported an association between EGFR mutations and the amount and duration of cigarette smoking, with the highest incidence of mutations seen in never smokers. Methods EGFR exon 19 and 21 mutation status was determined in 265 tumor samples using direct sequencing, polymerase chain reaction (PCR), or PCR-based restriction fragment length polymorphism analysis. A detailed smoking history was obtained. Patients were categorized as never smokers (< 100 lifetime cigarettes), former smokers (quit ≥ 1 year ago), or current smokers (quit < 1 year ago). Results We detected EGFR mutations in 34 (51%) of 67 never smokers (95% CI, 38% to 64%), 29 (19%) of 151 former smokers (95% CI, 13% to 27%), and two (4%) of 47 current smokers (95% CI, 1% to 16%). Significantly fewer EGFR mutations were found in people who smoked for more than 15 pack-years (P < .001) or stopped smoking less than 25 years ago (P < .02) compared with individuals who never smoked. The number of smoking pack-years and smoke-free years predicted the prevalence of EGFR mutations (areas under receiver operating characteristic curve = 0.78 and 0.77, respectively). Conclusion The likelihood of EGFR mutations in exons 19 and 21 decreases as the number of pack-years increases. Mutations were less common in people who smoked for more than 15 pack-years or who stopped smoking cigarettes less than 25 years ago. These data can assist clinicians in assessing the likelihood of exon 19 and 21 EGFR mutations in patients with lung adenocarcinoma when mutational analysis is not feasible.

scholarly journals Brain metastases in lung adenocarcinoma: impact of EGFR mutation status on incidence and survival

2014 ◽  
Vol 48 (2) ◽  
pp. 173-183 ◽  
Author(s):  
Karmen Stanic ◽  
Matjaz Zwitter ◽  
Nina Turnsek Hitij ◽  
Izidor Kern ◽  
Aleksander Sadikov ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Lung Adenocarcinoma ◽  
Cumulative Incidence ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Mutation Status ◽  
Course Of Disease ◽  
Epidermal Growth ◽  
Egfr Mutant

AbstractBackground. The brain represents a frequent progression site in lung adenocarcinoma. This study was designed to analyse the association between the epidermal growth factor receptor (EGFR) mutation status and the frequency of brain metastases (BM) and survival in routine clinical practice.Patients and methods. We retrospectively analysed the medical records of 629 patients with adenocarcinoma in Slovenia who were tested for EGFR mutations in order to analyse the cumulative incidence of BM, the time from the diagnosis to the development of BM (TDBM), the time from BM to death (TTD) and the median survival.Results. Out of 629 patients, 168 (27%) had BM, 90 patients already at the time of diagnosis. Additional 78 patients developed BM after a median interval of 14.3 months; 25.8 months in EGFR positive and 11.8 months in EGFR negative patients, respectively (p = 0.002). EGFR mutations were present in 47 (28%) patients with BM. The curves for cumulative incidence of BM in EGFR positive and negative patients demonstrate a trend for a higher incidence of BM in EGFR mutant patients at diagnosis (19% vs. 13%, p = 0.078), but no difference later during the course of the disease. The patients with BM at diagnosis had a statistically longer TTD (7.3 months) than patients who developed BM later (3.1 months). The TTD in EGFR positive patients with BM at diagnosis was longer than in EGFR negative patients (12.6 vs. 6.8, p = 0.005), while there was no impact of EGFR status on the TTD of patients who developed BM later.Conclusions. Except for a non-significant increase of frequency of BM at diagnosis in EGFR positive patients, EGFR status had no influence upon the cumulative incidence of BM. EGFR positive patients had a longer time to CNS progression. While EGFR positive patients with BM at diagnosis had a longer survival, EGFR status had no influence on TTD in patients who developed BM later during the course of disease.

Impact of HER2 aberrations on EGFR-TKI treatment outcomes in lung tumors harboring EGFR mutations: A HER2-CS STUDY subset analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9056-9056 ◽  
Author(s):  
Hiroe Kayatani ◽  
Keisuke Aoe ◽  
Kadoaki Ohashi ◽  
Hiroshige Yoshioka ◽  
Akihiro Bessho ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Her2 Protein ◽  
Epidermal Growth ◽  
Tki Treatment ◽  
Egfr Mutant ◽  
Egfr Mutated ◽  
Egfr Tki ◽  
Egfr Tkis

9056 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a key treatment for EGFR-mutated non-small-cell lung carcinoma (NSCLC). To date, a biomarker to predict whether NSCLC will exhibit a short- or long-term response to first- or second-generation EGFR-TKIs has not been established for clinical use. Human epidermal growth factor receptor-2 (HER2) aberrations are mechanisms for acquired resistance to EGFR-TKIs; however, their impact on EGFR-TKI therapy outcomes in EGFR-mutant NSCLC has not yet been systematically evaluated. Methods: Patients with advanced NSCLC were prospectively registered from more than 35 institutes (HER2-CS STUDY UMIN 000017003). EGFR mutations or anaplastic lymphoma kinase gene translocations were assessed at each institution using a commercially approved test. HER2 protein expression levels were determined by immunohistochemistry (IHC) using the Ventana I-VIEW PATHWAY anti-HER-2/neu (4B5). The IHC status scoring system applied to gastric cancer was used. Results: Of 1,126 screened patients with NSCLC, 354 (31.8%) had EGFR-mutated tumors, and the HER2 protein statuses were as follows: IHC0 (n = 71, 26%), IHC1+ (n = 148, 53%), IHC2+ (n = 51, 18%), and IHC3+ (n = 7, 3%). The patients’ demographics were almost identical in those with lung tumors harboring EGFR mutations and HER2-IHC2+/3+ (group P) or EGFR mutations and HER2-IHC0/1 (group N). The EGFR-TKI response rates were not different between these groups (Table). However, group P showed significantly shorter time to EGFR-TKI treatment failure than group N (median 19.1 vs. 13.3 months; log rank p = 0.038). Conclusions: These data from a large prospective cohort show that HER2 protein expression in EGFR-mutant NSCLC may have a negative impact on the effect of EGFR-TKIs. A clinical trial of EGFR/HER2-TKIs (e.g., afatinib) is warranted for this population. [Table: see text]

Impact of epidermal growth factor receptor mutations on intracranial treatment response and survival after brain metastases in lung adenocarcinoma patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19030-e19030
Author(s):  
Shih-Hsin Hsiao ◽  
Horng-Chyuan Lin ◽  
Ming-Chih Yu ◽  
Chi-Li Chung
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Lung Adenocarcinoma ◽  
Treatment Response ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Wild Type ◽  
Epidermal Growth ◽  
Egfr Mutant

e19030 Background: Brain metastases (BM) commonly occur in patients with lung adenocarcinoma and usually lead to a poor prognosis. Epidermal growth factor receptor (EGFR) mutation is a predictive and prognostic factor for EGFR tyrosine kinase inhibitor (TKI) treatment for lung adenocarcinoma. The present study aimed to elucidate the predictive role of EGFR mutations in BM treatment response and survival after BM in patients with lung adenocarcinoma patients. Methods: From January 2006 through February 2012, 180 of 505 lung adenocarcinoma patients developed BM during their disease course were reviewed for eligibility, and 139 patients, including 89 EGFR mutant and 50 EGFR wild-type patients, were identified for analysis. BM treatment response was assessed radiologically 1 month after start of treatment and survival data was collected. Results: EGFR mutant patients, compared with EGFR wild-type patients, had significantly greater treatment response of BM (85% vs. 53%, P = 0.001) and longer median survival after BM diagnosis (13.2 vs. 6.8 months, P < 0.001). EGFR mutation (P = 0.001) and use of EGFR TKI during treatment (P = 0.037) were independently associated with BM treatment response. Furthermore, EGFR mutation (P = 0.005), good performance status (P < 0.001) and absence of extracranial metastases (P = 0.033) correlated with better survival. Conclusions: EGFR mutation is an independent predictive factor for both BM treatment response and survival after BM in patients with lung adenocarcinoma. Further studies on incorporation of EGFR mutation status into therapeutic strategy and survival prediction system for lung adenocarcinoma with BM are warranted.

Liver endothelium promotes HER3-mediated cell survival in KRAS wild-type and mutant colorectal cancer cells

2021 ◽  
Author(s):  
Moeez Rathore ◽  
Michel'le Wright ◽  
Rajat Bhattacharya ◽  
Fan Fan ◽  
Ali Vaziri-Gohar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Survival ◽  
Growth Factor Receptor ◽  
Wild Type ◽  
Mutation Status ◽  
Her Family ◽  
Epidermal Growth

Abstract We previously showed that human epidermal growth factor receptor 3 (HER3, also known as ERBB3) is a key mediator in liver endothelial cell (EC) promoting colorectal cancer (CRC) growth and chemoresistance, and suggested HER3-targeted therapy as a strategy for treating patients with metastatic CRC (mCRC) in the liver. Meanwhile, KRAS mutations occur in 40–50% of mCRC and render CRC resistant to therapies targeting the other HER family protein epidermal growth factor receptor (EGFR). It is necessary to elucidate the roles of KRAS mutation status in HER3-mediated cell survival and CRC response to HER3 inhibition. In the present study, we demonstrated that liver EC-secreted factors activated HER3 and promoted cell survival in KRAS wild-type and mutant CRC cells and tumors, and that blocking HER3 with an antibody, seribantumab, blocked EC-induced CRC survival. Our findings highlight a potential of utilizing HER3-targeted therapies for treating patients with mCRC regardless of KRAS mutation status.

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