First-Line Focus: Molecular Testing and Guideline-Directed Therapy in EGFR-Positive NSCLC

Author(s):

Cara Chang, PharmD, BCOP

A panelist discusses how waiting for molecular testing results before initiating treatment for non–small cell lung cancer (NSCLC) is crucial because patients with EGFR mutations can avoid chemotherapy and immunotherapy in favor of targeted oral agents like osimertinib, which offer survival benefits with minimal toxicity compared to traditional treatments, while premature immunotherapy could cause severe immune-related adverse events that might preclude later use of more appropriate targeted therapies.

EP: 1.Overcoming Challenges in NSCLC Management From a Pharmacist’s Perspective

Now Viewing

EP: 2.First-Line Focus: Molecular Testing and Guideline-Directed Therapy in EGFR-Positive NSCLC

Molecular Testing and Treatment Selection in NSCLC: Guidelines for Physicians

Importance of Pre-Treatment Molecular Testing

Critical priority: Avoid hastily initiating treatment before obtaining molecular testing results
Standard treatment for NSCLC without targetable mutations is combination chemotherapy and immunotherapy
Starting treatment prematurely may expose patients to unnecessary toxicities and complicate subsequent therapeutic options

EGFR-Positive NSCLC Treatment Considerations

EGFR-positive patients can receive single oral targeted therapy as primary treatment, avoiding chemotherapy and immunotherapy
First-line EGFR agents like osimertinib offer:
Improved survival benefits

Excellent central nervous system penetration

Minimal comparative toxicity
Warning: Starting immunotherapy prior to osimertinib in EGFR-positive patients may:
Increase risk of severe immune-related adverse events

Preclude osimertinib use until immunotherapy is completely cleared

Guideline Comparison: ASCO vs NCCN

ASCO Guidelines

EGFR Exon 19 deletion/Exon 21 L858R substitution:
Primary recommendation: Osimertinib monotherapy

Alternative consideration: Osimertinib with chemotherapy
Atypical EGFR mutations:
Weaker recommendation for afatinib or osimertinib
EGFR Exon 20 insertion:
Chemotherapy and amivantamab, or standard non–driver alteration treatments

NCCN Guidelines

Generally broader recommendations, including all FDA-approved options
EGFR Exon 19 deletion/Exon 21 L858R:
Multiple options: afatinib, erlotinib, dacomitinib, gefitinib, osimertinib with chemotherapy, or amivantamab plus lazertinib
Atypical EGFR mutations:
Any monotherapy EGFR tyrosine kinase inhibitors without preference between afatinib or osimertinib
EGFR Exon 20 insertion:
Similar to ASCO: amivantamab plus chemotherapy as first-line recommendation