High-Dose Furmonertinib Management of Advanced NSCLC Harboring an EGFR Exon 14 Missense Mutation: A Case Report and...

Area of Science:

• Oncology
• Genetics
• Pharmacology

Background:

• Epidermal growth factor receptor (EGFR) mutations are key drivers in non-small-cell lung cancer (NSCLC).
• Standard EGFR tyrosine kinase inhibitors (TKIs) are effective for common mutations like exon 19 deletion and L858R.
• Optimal treatment for rare EGFR exon 14 mutations in NSCLC is currently undefined.

Purpose of the Study:

• To report a case of advanced NSCLC with acquired EGFR exon 14 missense mutation.
• To investigate the potential efficacy of high-dose furmonertinib in this rare mutation setting.

Main Methods:

• A patient with advanced NSCLC initially treated for EGFR exon 21 L858R mutation experienced disease progression.
• Next-generation sequencing (NGS) revealed loss of L858R and emergence of an EGFR exon 14 missense mutation.
• High-dose furmonertinib was administered sequentially at escalating doses (160 mg, 200 mg, 240 mg qd).

Main Results:

• The patient received high-dose furmonertinib for at least 20 months after detecting the exon 14 mutation.
• Disease progression occurred despite initial and second-line TKI treatments.
• The patient was eventually admitted to the ICU for infection-related respiratory failure.

Conclusions:

• This single case suggests a potential role for high-dose furmonertinib in NSCLC with EGFR exon 14 missense mutations.
• The study's findings are limited by confounding factors and do not confirm efficacy.
• Further clinical investigation is necessary to validate high-dose furmonertinib for this specific NSCLC subtype.