From the Guidelines
EGFR 72 refers to a mutation in the epidermal growth factor receptor (EGFR) gene at exon 20, specifically at position 72, and for patients with this mutation, targeted therapies such as amivantamab (Rybrevant) or mobocertinib (Exkivity) are recommended as first-line treatment options. This mutation is clinically significant in non-small cell lung cancer (NSCLC) patients. The recommended treatment options include amivantamab (Rybrevant) at 1050 mg for patients <80 kg or 1400 mg for patients ≥80 kg administered intravenously weekly for the first 4 weeks, then biweekly thereafter, or mobocertinib (Exkivity) 160 mg orally once daily 1. These targeted therapies are preferred over standard chemotherapy as they specifically address the molecular driver of the cancer. First-generation EGFR tyrosine kinase inhibitors like erlotinib, gefitinib, and afatinib typically have limited efficacy against exon 20 insertion mutations.
Key Considerations
- Treatment should be continued until disease progression or unacceptable toxicity.
- Common side effects include rash, diarrhea, and paronychia, which should be managed proactively.
- Regular monitoring with CT scans every 2-3 months is recommended to assess treatment response.
- EGFR mutations drive cancer growth by constitutively activating signaling pathways that promote cell proliferation and survival, and targeted therapies work by specifically inhibiting these aberrant pathways.
Management of Adverse Events
The management of adverse events associated with EGFR tyrosine kinase inhibitors is crucial to maintain the quality of life of patients and to avoid premature discontinuation of these drugs 1. Supportive care, dose reductions, and treatment interruptions are appropriate strategies to manage EGFR-TKI-associated adverse events. Patients should be followed up closely, especially during the first 6 weeks of treatment, to promptly address any adverse events that may arise.
Clinical Guidelines
Clinical guidelines recommend testing patients with NSCLC for EGFR mutations at the time of diagnosis whenever feasible, and treating with first-line EGFR TKIs if mutation positive 1. The National Comprehensive Cancer Network (NCCN) guidelines also provide recommendations for the management of NSCLC with EGFR alterations, including the use of targeted therapies for patients with exon 20 insertion mutations 1.
From the Research
EGFR Mutations
- EGFR mutations are a predictive factor for response to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) patients 2, 3, 4, 5, 6
- The most common activating EGFR mutations are in-frame deletion in exon 19 and point mutation in exon 21, which account for 90% of EGFR mutations 2, 5, 6
Treatment Strategies
- EGFR-TKIs are the standard of care for patients with metastatic NSCLC and activating EGFR mutations 3, 4, 5
- Osimertinib is considered the best EGFR-TKI for front-line therapy, while other agents like dacomitinib and new drug combinations may be potential alternatives 4
- The introduction of osimertinib provides an opportunity to overcome T790M-mediated resistance to first-generation and second-generation EGFR-TKIs 3
Prognostic Implications
- Patients with exon 19 deletion (Del19) and exon 21 L858R substitution (L858R) have distinct prognostic implications and may require individual therapeutic strategies 6
- EGFR-TKIs provide a significant overall survival benefit in patients with Del19 compared to those with L858R 6
Uncommon EGFR Mutations
- Uncommon EGFR mutations, such as G719X, L861Q, and S768I, have variable sensitivity to different EGFR-TKIs and require further study to determine the best treatment strategies 2, 4
- The paucity of prospective clinical data and the wide heterogeneity of uncommon mutations complicate treatment decisions in this patient subgroup 2