What does elevated Epidermal Growth Factor Receptor (EGFR) mean?

From the Guidelines

Elevated EGFR typically refers to an overexpression or mutation of the Epidermal Growth Factor Receptor, which is often associated with non-small cell lung cancer (NSCLC) and can indicate a potential responsiveness to EGFR tyrosine kinase inhibitor (TKI) therapy. The EGFR gene mutations are commonly found in patients with NSCLC, with the most commonly described mutations being deletions in exon 19 and a mutation in exon 21, which result in activation of the tyrosine kinase domain and are associated with sensitivity to TKIs 1. These sensitizing EGFR mutations are found in approximately 10% of Caucasian patients with NSCLC and up to 50% of Asian patients.

Some key points to consider when evaluating elevated EGFR include:

• The presence of sensitizing EGFR mutations, such as exon 19 deletions and exon 21 L858R point mutation, which are associated with responsiveness to EGFR TKI therapy 1
• The presence of less common EGFR mutations, such as exon 19CE insertions, p.L861Q, p.G719X, and p.S768I, which may also be associated with responsiveness to EGFR TKI therapy, although the number of studied patients is lower 1
• The presence of EGFR exon 20 insertion mutations, which are associated with resistance to clinically achievable levels of TKIs, with the exception of a rare EGFR exon 20 insertion variant, p.A763_Y764insFQEA, which is associated with responsiveness to EGFR TKI therapy 1
• The finding of p.T790M, which is most commonly associated with relapse following initial therapy with EGFR TKI and is a known mechanism of resistance 1

In terms of treatment, patients with elevated EGFR due to sensitizing mutations may benefit from EGFR TKI therapy, such as erlotinib, gefitinib, or afatinib, as first-line treatment for metastatic NSCLC 1. However, patients with primary resistance to TKI therapy, such as those with KRAS mutations or ALK or ROS1 gene rearrangements, may not benefit from EGFR TKI therapy.

It's also important to note that elevated EGFR can have different implications depending on the context, and a thorough evaluation by a healthcare provider is necessary to determine the underlying cause and appropriate treatment. Regular medical check-ups and maintaining good hydration are advisable, especially if you have risk factors for kidney disease or other underlying conditions that may be associated with elevated EGFR.

From the FDA Drug Label

Epidermal growth factor receptor (EGFR) is expressed on the cell surface of both normal and cancer cells. The FDA drug label does not answer the question.

From the Research

Definition of Elevated EGFR

Elevated levels of the epidermal growth factor receptor (EGFR) refer to an increase in the expression of this growth-factor-receptor tyrosine kinase, which can be associated with various types of cancer, including non-small cell lung cancer (NSCLC) 2.

Association with Cancer

The elevated EGFR levels have been identified as a common component of multiple cancer types and appear to promote solid tumor growth 2. The EGFR was found to act as a strong prognostic indicator in head and neck, ovarian, cervical, bladder, and oesophageal cancers, where increased EGFR expression was associated with reduced recurrence-free or overall survival rates in 70% of studies 2.

EGFR Mutations in NSCLC

In NSCLC, EGFR mutations can lead to the activation of the EGFR signaling pathway, which can result in increased cell proliferation and survival 3. The Tumor Microenvironment (TME) of patients with NSCLC harboring EGFR mutations displays peculiar characteristics and may modulate the antitumor immune response 3.

Treatment Options

Several treatment options are available for patients with EGFR-mutated NSCLC, including EGFR-Tyrosine Kinase Inhibitors (TKIs) such as osimertinib, erlotinib, and gefitinib 4, 5, 6. These treatments have shown efficacy and safety in improving overall response rate and disease control in patients with EGFR-mutated advanced NSCLC 4.

Key Points

• Elevated EGFR levels are associated with various types of cancer, including NSCLC 2
• EGFR mutations can lead to the activation of the EGFR signaling pathway, resulting in increased cell proliferation and survival 3
• Several treatment options are available for patients with EGFR-mutated NSCLC, including EGFR-TKIs such as osimertinib, erlotinib, and gefitinib 4, 5, 6
• These treatments have shown efficacy and safety in improving overall response rate and disease control in patients with EGFR-mutated advanced NSCLC 4