Case Report: Dacomitinib May Not Benefit Patients Who Develop Rare Compound Mutations After Later-Line Osimertinib...

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Osimertinib resistance in EGFR-mutated lung adenocarcinoma is a significant clinical challenge.
• Acquired EGFR C797X mutations are common resistance mechanisms.
• Novel secondary EGFR mutations at L718 and L792 residues also confer osimertinib resistance.

Observation:

• Five lung adenocarcinoma patients with osimertinib resistance were identified.
• Targeted next-generation sequencing revealed recurrent EGFR L792 and/or L718 mutations in these patients.
• Dacomitinib treatment was initiated post-osimertinib resistance.

Findings:

• All five patients experienced disease progression within two months of dacomitinib treatment.
• Molecular structural simulations indicated that L792H + T790M and L718Q mutations interfere with dacomitinib binding to EGFR.
• These complex mutations may confer primary resistance to dacomitinib.

Implications:

• This case series is the first to report on the clinical efficacy of dacomitinib in patients with rare complex EGFR mutations post-osimertinib resistance.
• The findings suggest dacomitinib may not be an effective treatment option for patients with these specific resistance mutations.
• Further research is needed to identify effective therapeutic strategies for patients with osimertinib-resistant EGFR-mutated lung adenocarcinoma harboring complex secondary mutations.