What are Epidermal Growth Factor Receptor (EGFR) cancers?

From the Guidelines

EGFR tyrosine kinase inhibitors (TKIs) are the recommended first-line treatment for patients with confirmed EGFR mutations in non-small cell lung cancer (NSCLC). The most recent and highest quality study, 1, supports the use of EGFR TKIs, such as erlotinib, gefitinib, and afatinib, as first-line therapy for patients with EGFR-mutant advanced NSCLC. These targeted therapies have been shown to have a higher response rate, delayed progression, and improved quality of life compared to traditional chemotherapy.

Key Points

• EGFR TKIs, including erlotinib (150mg daily) and gefitinib (250mg daily), are effective in treating EGFR-mutant NSCLC
• Second-generation options like afatinib (40mg daily) and third-generation osimertinib (80mg daily) are also available
• Treatment continues until disease progression or unacceptable toxicity
• Side effects typically include skin rash, diarrhea, and rarely, pneumonitis
• Regular monitoring with imaging every 2-3 months is recommended to assess treatment response

Management of Adverse Events

• Cutaneous adverse events can be prevented with regular use of emollients, and dose reduction or interruption of the EGFR-TKI may be necessary if grade 2 toxicity is prolonged or intolerable 2
• Diarrhea can be managed with a low-fat, low-fiber diet, and loperamide, together with oral isotonic solution, is indicated for diarrhea persisting >48 hours 2

EGFR Testing

• EGFR testing is essential before starting therapy, usually performed on tumor tissue or liquid biopsy
• The test results will guide the treatment decision, with EGFR TKIs being the preferred treatment for patients with confirmed EGFR mutations 3

From the FDA Drug Label

Epidermal growth factor receptor (EGFR) is expressed on the cell surface of both normal and cancer cells. In some tumor cells signaling through this receptor plays a role in tumor cell survival and proliferation irrespective of EGFR mutation status Erlotinib reversibly inhibits the kinase activity of EGFR, preventing autophosphorylation of tyrosine residues associated with the receptor and thereby inhibiting further downstream signaling. Erlotinib binding affinity for EGFR exon 19 deletion or exon 21 (L858R) mutations is higher than its affinity for the wild type receptor.

Erlotinib is used to treat EGFR cancers by inhibiting the kinase activity of the EGFR receptor. The drug has a higher binding affinity for EGFR exon 19 deletion or exon 21 (L858R) mutations than for the wild-type receptor.

• Key points: + Erlotinib inhibits EGFR kinase activity + Higher binding affinity for EGFR exon 19 deletion or exon 21 (L858R) mutations + Used to treat EGFR cancers 4

From the Research

EGFR Cancers Overview

• EGFR (Epidermal Growth Factor Receptor) cancers are a type of non-small cell lung cancer (NSCLC) that have mutations in the EGFR gene.
• These mutations can lead to uncontrolled cell growth and cancer development.

Treatment Options

• Several treatment options are available for EGFR-mutated NSCLC, including: + EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib, erlotinib, and afatinib 5, 6, 7 + Osimertinib, a third-generation EGFR-TKI, which has shown improved efficacy and safety compared to first-generation EGFR-TKIs 8, 9
• The choice of treatment depends on various factors, including the type of EGFR mutation, disease stage, and patient characteristics.

Efficacy and Safety of EGFR-TKIs

• Studies have shown that EGFR-TKIs are effective in improving progression-free survival (PFS) and overall response rate (ORR) in patients with EGFR-mutated NSCLC 5, 6, 7, 9
• Osimertinib has been shown to have a higher ORR and disease control rate compared to erlotinib and gefitinib 9
• EGFR-TKIs are generally well-tolerated, with common adverse events including rash, diarrhea, and fatigue 5, 6, 7

Real-World Treatment Patterns and Outcomes

• A retrospective analysis of real-world treatment patterns and outcomes in patients with EGFR-mutated NSCLC found that over a quarter of patients died before initiating second-line treatment, and half of patients progressed after first-line treatment 8
• The study also found that disease stage, performance status, and central nervous system metastasis were significant predictors of survival.

Comparison of EGFR-TKIs

• A meta-analysis comparing the efficacy and safety of osimertinib, erlotinib, and gefitinib as first-line treatment for EGFR-mutated NSCLC found that all three EGFR-TKIs were effective and safe, but osimertinib had a higher ORR and disease control rate compared to erlotinib and gefitinib 9