The impact of epidermal growth factor receptor mutations on patterns of disease recurrence after chemoradiotherapy for locally advanced non–small cell lung cancer: a literature review and pooled analysis

Abstract The purpose of this review was to evaluate the impact of epidermal growth factor receptor (EGFR) mutation status on disease recurrence in patients treated with chemoradiotherapy (CRT) for locally advanced non–small cell lung cancer (NSCLC). A literature search was conducted and a total of three studies were analyzed. There was no significant difference in the objective response rate between the EGFR mutation group and the EGFR wild-type group (odds ratios [OR] 1.46, 95% CI, 0.79–2.70, P = 0.228), and there was no significant difference in the incidence of disease recurrence (OR 1.37, 95% CI, 0.68–2.75, P = 0.379) between the two groups. There were significant difference in the incidence of local/locoregional progression (LP) (OR 0.35, 95% CI, 0.18–0.71, P = 0.003) and distant progression (DP) (OR 2.97, 95% CI, 1.59–5.54, P < 0.001). Brain metastasis (BM) was one of the main recurrence patterns of DP, and the incidence was significantly higher in the EGFR mutant group (OR 2.75, 95% CI, 1.43–5.31, P = 0.003). There were no statistically significant heterogeneities in these pooled analyses. The patterns of recurrence after CRT for locally advanced NSCLC were different according to EGFR mutation status. LP after CRT in patients with EGFR mutation was less frequent, but the high incidence of DP, especially BM, continued to be the major problem. On the other hand, LP continued to be the major problem in EGFR wild-type patients. In multimodality treatment for inoperable locally advanced NSCLC, we may need to consider different treatment strategies according to EGFR mutation status.

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Cross-Validation Study for Epidermal Growth Factor Receptor and KRAS Mutation Detection in 74 Blinded Non-small Cell Lung Carcinoma Samples: A Total of 5550 Exons Sequenced by 15 Molecular French Laboratories (Evaluation of the EGFR Mutation Status for the Administration of EGFR-TKIs in Non-Small Cell Lung Carcinoma [ERMETIC] Project—Part 1)

Journal of Thoracic Oncology ◽

10.1097/jto.0b013e318211dcee ◽

2011 ◽

Vol 6 (6) ◽

pp. 1006-1015 ◽

Cited By ~ 43

Author(s):

Michèle Beau-Faller ◽

Armelle Degeorges ◽

Estelle Rolland ◽

Mounia Mounawar ◽

Martine Antoine ◽

...

Keyword(s):

Lung Carcinoma ◽

Egfr Mutation ◽

Small Cell Lung Carcinoma ◽

Growth Factor Receptor ◽

Small Cell ◽

Small Cell Lung ◽

Cell Lung Carcinoma ◽

Mutation Status ◽

Epidermal Growth ◽

Egfr Tkis

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

Radiology and Oncology ◽

10.2478/raon-2014-0016 ◽

2014 ◽

Vol 48 (2) ◽

pp. 173-183 ◽

Cited By ~ 31

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.

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Impact of dietary habits on epidermal growth factor receptor (EGFR) mutation status of Japanese patients with lung adenocarcinomas.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.1567 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. 1567-1567

Author(s):

Y. Yamane ◽

M. Iwasaki ◽

A. Kawase ◽

K. Tsuchihara ◽

G. Ishii ◽

...

Keyword(s):

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Egfr Mutation ◽

Dietary Habits ◽

Growth Factor Receptor ◽

Japanese Patients ◽

Mutation Status ◽

Epidermal Growth ◽

Lung Adenocarcinomas

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

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e19030 ◽

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.

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

10.21203/rs.3.rs-745208/v1 ◽

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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The Impact of Clinical Outcomes According to EGFR Mutation Status in Patients with Locally Advanced Lung Adenocarcinoma Who Recieved Concurrent Chemoradiotherapy

American Journal of Clinical Oncology ◽

10.1097/coc.0b013e31826e04f9 ◽

2014 ◽

Vol 37 (2) ◽

pp. 144-147 ◽

Cited By ~ 20

Author(s):

Hiroaki Akamatsu ◽

Kyoichi Kaira ◽

Haruyasu Murakami ◽

Masakuni Serizawa ◽

Yasuhiro Koh ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Clinical Outcomes ◽

Concurrent Chemoradiotherapy ◽

Egfr Mutation ◽

Locally Advanced ◽

Mutation Status ◽

The Impact

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The impact of epidermal growth factor receptor mutations on the efficacy of definitive chemoradiotherapy in patients with locally advanced unresectable stage III non-small cell lung cancer: a systematic review and meta-analysis

Expert Review of Anticancer Therapy ◽

10.1080/14737140.2019.1621754 ◽

2019 ◽

Vol 19 (6) ◽

pp. 533-539

Author(s):

Qin Qin ◽

Bing Peng ◽

Baosheng Li

Keyword(s):

Lung Cancer ◽

Meta Analysis ◽

Locally Advanced ◽

Growth Factor Receptor ◽

Small Cell ◽

Small Cell Lung ◽

Definitive Chemoradiotherapy ◽

Unresectable Stage ◽

Epidermal Growth ◽

The Impact

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Nicht kleinzelliges Lungenkarzinom: Angiogenese-Hemmer als weiteres entscheidendes Element in der Behandlung

Karger Kompass Pneumologie ◽

10.1159/000512162 ◽

2020 ◽

Vol 8 (6) ◽

pp. 318-319

Author(s):

Susanne M. Lang ◽

Tobias Rachow

Keyword(s):

Combination Therapy ◽

Egfr Mutation ◽

Growth Factor Receptor ◽

Progression Free Survival ◽

Kleinzelliges Lungenkarzinom ◽

Driver Mutations ◽

Wild Type ◽

Mutation Status ◽

Type Group ◽

Egfr Mutant

Objectives: Currently, combination therapy of ramucirumab (RAM) + docetaxel (DOC) must play a more important role as a second-line treatment. Epithelial growth factor receptor (EGFR) mutation accounts for around 50% of oncogenic driver mutations in patients with advanced non-small cell lung cancer (NSCLC) in Asian subsets. The number of brain metastases (BM) is relatively higher in EGFR mutation-positive patients compared to EGFR wild-type patients. The objective of this study is to evaluate the efficacy of RAM + DOC focusing on EGFR mutation and BM. Methods: We retrospectively reviewed consecutive advanced NSCLC patients who received combination therapy of RAM + DOC at three institutions. A total of 112 patients with NSCLC were enrolled for efficacy analyses. We evaluated the efficacy of RAM + DOC for EGFR-mutated NSCLC with endpoints including progression-free survival (PFS), time to treatment failure (TTF) and overall survival. Results: Median PFS was 5.7 months for the EGFR mutant group compared with 3.6 months for the EGFR wild-type group (HR 0.53, 95% CI 0.32–0.87; p = 0.01). Median TTF was 5.1 months for the EGFR mutant group compared with 2.8 months for the EGFR wild-type group (HR 0.53, 95% CI 0.33–0.85; p = 0.007). Median PFS and TTF of the EGFR mutant group was significantly longer than median PFS and TTF of the EGFR wild-type group. The multivariate analysis identified EGFR mutation status as an independent favorable factor of PFS. In subset analyses of BM, median PFS of the EGFR mutant group (2.8 months) was significantly shorter than that of the EGFR wild-type group (5.1 months) (HR 7.27, 95% CI 1.78–29.68; p = 0.002). Conclusion: This study revealed that EGFR mutation status and BM might be predictive or prognostic factors for PFS.

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