Article Details

Epidermal growth factor receptor (EGFR) mutations are major driver oncogenes in non-small cell lung cancer (NSCLC). While classical mutations account for the vast majority of cases, uncommon EGFR mutations such as exon 21 L861Q represent a clinically heterogeneous subgroup with historically variable responsiveness to targeted therapies. Here, we report a 68-year-old non-smoking female who presented with progressive cough and dyspnea and was diagnosed with Stage IVA lung adenocarcinoma. Targeted next-generation sequencing (NGS) of biopsy tissue revealed an isolated uncommon EGFR L861Q point mutation without concurrent classical mutations or resistance markers. The patient was initiated on first-line oral osimertinib at 80 mg once daily, achieving a rapid partial response with over 60% tumor regression at 8 weeks alongside complete symptomatic relief. The patient maintained continuous, durable disease control for 18 months with excellent functional status and minimal treatment-related toxicity. This case highlights the high therapeutic efficacy and favorable safety profile of third-generation EGFR TKIs like osimertinib in NSCLC harboring uncommon EGFR L861Q mutations, underscoring the vital role of broad molecular profiling in guiding precision oncology decisions.

Keywords: Non-small cell lung cancer (NSCLC); EGFR Exon 21 L861Q mutation; Osimertinib; Targeted therapy