What treatment options are available for a patient with low Epidermal Growth Factor Receptor (EGFR) levels?

Treatment Options for Low EGFR Expression in Non-Small Cell Lung Cancer

For patients with low EGFR expression levels, platinum-based chemotherapy is recommended as the standard of care treatment, as EGFR tyrosine kinase inhibitors are not effective in EGFR wild-type NSCLC. 1

Understanding EGFR Status and Treatment Implications

• EGFR mutations are present in approximately 10% of Caucasian patients with NSCLC and are more common in never-smokers, adenocarcinoma subtypes, women, and East-Asian populations 2
• EGFR mutation testing is recommended in all patients with advanced NSCLC of non-squamous subtype before initiating first-line treatment 2
• Low EGFR expression (EGFR wild-type) indicates absence of sensitizing EGFR mutations, making these tumors unresponsive to EGFR tyrosine kinase inhibitors (TKIs) 1

First-Line Treatment Recommendations for EGFR Wild-Type NSCLC

• For patients with performance status 0-1 and EGFR wild-type NSCLC, a platinum-based two-drug combination of cytotoxic drugs is recommended 2
• Nonplatinum cytotoxic doublets are acceptable alternatives for patients with contraindications to platinum therapy 2
• For patients with performance status 2, a single cytotoxic drug is sufficient 2
• Platinum-based chemotherapy has been proven to prolong survival, improve symptom control, and yield superior quality of life compared to best supportive care in EGFR wild-type patients 2

Treatment Duration and Monitoring

• First-line cytotoxic chemotherapy should be stopped at disease progression or after four cycles in patients who are not responding to treatment 2
• Two-drug cytotoxic chemotherapy should be stopped at six cycles even in patients who are responding to therapy 2
• Maintenance therapy with pemetrexed may be considered for patients with non-squamous histology who have achieved tumor stabilization or response after first-line chemotherapy 2

Second-Line Treatment Options

• For patients progressing after first-line chemotherapy with performance status 0-2, recommended second-line options include:
  • Docetaxel (for all histologies) 2
  • Pemetrexed (for non-squamous histology only) 2
  • Immune checkpoint inhibitors (nivolumab, pembrolizumab, or atezolizumab) which are preferred over cytotoxic chemotherapy due to improved survival rates, longer duration of response, and fewer adverse events 2

Important Considerations and Caveats

• Avoid using EGFR TKIs in EGFR wild-type patients as first-line therapy as they show inferior efficacy compared to chemotherapy 1
• EGFR TKIs (erlotinib) may be considered as a third-line option for EGFR wild-type patients who have not previously received EGFR TKIs and are not eligible for further chemotherapy 2
• PD-1/PD-L1 inhibitor monotherapy should be considered over EGFR TKIs in subsequent lines of therapy for EGFR wild-type NSCLC due to superior efficacy 3
• Comprehensive molecular testing is crucial to identify other potentially targetable alterations that might be present even in EGFR wild-type tumors 2

Special Situations

• For patients with brain metastases, consider stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT) as EGFR TKIs have limited efficacy in EGFR wild-type disease 2
• In patients with oligometastatic disease (1-3 metastases), consider definitive local therapy (stereotactic ablative radiotherapy or surgery) as consolidation after systemic therapy 3
• For patients with poor performance status (PS 3-4) who are not candidates for cytotoxic chemotherapy, best supportive care and early integration of palliative care should be prioritized 1