scholarly journals HER2 Aberrations in Non-Small Cell Lung Cancer: From Pathophysiology to Targeted Therapy

2021 ◽  
Vol 14 (12) ◽  
pp. 1300
Author(s):  
Ioannis A. Vathiotis ◽  
Andriani Charpidou ◽  
Niki Gavrielatou ◽  
Konstantinos N. Syrigos
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Clinical Trials ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Protein Overexpression ◽  
Small Cell Lung ◽  
Activating Mutations ◽  
Epidermal Growth

While human epidermal growth factor receptor 2 (HER2) aberrations have long been described in patients with non-small cell lung cancer (NSCLC), they have only recently been effectively targeted. Unlike patients with breast cancer, NSCLC patients can harbor either HER2-activating mutations or HER2 amplification coupled with protein overexpression. The latter has also been the case for patients with acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). As preclinical data continue to accumulate, clinical trials evaluating novel agents that target HER2 have produced promising preliminary results. Here, we review existing data on HER2 aberrations in NSCLC. Starting from HER2 biology in normal and disease processes, we summarize discrepancies in HER2 diagnostic assays between breast cancer and NSCLC. Finally, to dissect the therapeutic implications of HER2-activating mutations versus gene amplification and/or protein overexpression, we present data from prospective clinical trials that have employed distinct classes of agents to target HER2 in patients with NSCLC.

scholarly journals Irreversible tyrosine kinase inhibition of epidermal growth factor receptor with afatinib in EGFR activating mutation–positive advanced non-small-cell lung cancer

2018 ◽  
Vol 25 ◽  
pp. 9 ◽  
Author(s):  
S. Morin-Ben Abdallah ◽  
V. Hirsh
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
First Generation ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Activating Mutations ◽  
Epidermal Growth

Despite recent advances in the systemic therapy of non-small-cell lung cancer (nsclc), the prognosis for stage iv disease remains poor. The discovery of targetable mutations has led to new treatment options. The most common mutations, the EGFR activating mutations, are present in about 50% of Asian patients and up to 15% of white patients. First-generation reversible epidermal growth factor receptor (egfr) tyrosine kinase inhibitors (tkis) have led to improved survival in patients positive for EGFR activating mutations, but resistance eventually leads to disease progression. The irreversible egfr tki afatinib was developed to counter such resistance. The clinical efficacy of afatinib has been shown in first-line studies comparing it with both cytotoxic chemotherapy and first-generation egfr tkis. Afatinib has also shown continued benefit beyond progression while a patient is taking an egfr inhibitor. Furthermore, its toxicity profile is both predictable and manageable. The results of the principal clinical trials assessing afatinib are reviewed here.

The influence of gastric secretion inhibitors on gefitinib therapy in patients with non-small cell lung cancer harboring epidermal growth factor receptor activating mutations.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18059-e18059 ◽  
Author(s):  
Sho Saeki ◽  
Jiichiro Sasaki ◽  
Junko Morioka ◽  
Ryo Sato ◽  
Shinya Sakata ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Gastric Secretion ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Activating Mutations ◽  
Epidermal Growth

e18059 Background: Gefitinib is orally available, selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used in patients with non-small cell lung cancer (NSCLC), especially harboring EGFR activating mutations. Pharmacokinetic study revealed absorption of gefitinib was affected by the gastric pH. However, cancer patients in advanced stage are frequently administered gastric secretion inhibitors, such as proton pump inhibitors (PPIs) and H2 blockers (H2Bs) for various reasons. We hypothesized that gastric secretion inhibitors might suppress the efficacy of gefitinib therapy in NSCLC patients with EGFR activating mutations. The purpose of this study is to investigate the influence of PPIs/H2Bs on the efficacy of gefitinib therapy in the patients with NSCLC harboring EGFR activating mutations. Methods: From Apr 2004 to Aug 2011, we retrospectively analyzed the correlation between administration of PPIs/H2Bs and efficacy of gefitinib therapy in the patients with NSCLC harboring EGFR mutations. Results: Forty-three patients with EGFR mutations received gefitinib therapy in our hospital. 65.1% (28/43) patients administered PPIs/H2Bs simultaneously. Patients who received PPIs/H2Bs (PPIs/H2Bs group) had similar response rate compared with patients who didn’t receive PPIs/H2Bs (non-PPIs/H2Bs group) (77.8% vs 73.3%, p=1.00). Median progression free survival was 291 days in PPIs/H2Bs group and 353 days in non-PPIs/H2Bs group ( HR 1.23, Log-rank trest, p=0.578), respectively. Median overall survival was 718 days in PPIs/H2Bs group and not reached in non-PPIs/H2Bs group ( HR 1.53, Log-rank trest, p=0.403), respectively. Conclusions: Gastric secretion inhibitors didn’t affect the efficacy of gefitinib treatment in patients with NSCLC harboring EGFR activating mutations.

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