Stage 4A Lung Adenocarcinoma with Rare EGFR Exon 21 L861Q and Exon 18 G719A Co-Mutations Showing Complete PET-CT Response to Osimertinib: A Case Report.

Introduction: The most effective TKI choice for NSCLC carrying non-classical compound mutations in EGFR remains unclear. The compound mutation in exon 18 G719A and exon 21 L861Q is rare, and experience with osimertinib is limited. Case Presentation: A 51-year-old male patient underwent surgery for T4N0 colon adenocarcinoma in 2015 and was followed without recurrence after eight cycles of adjuvant CapeOx, which was observed in 2025. A right lung nodule that remained stable for 7 years showed dimensional progression from 1 cm to 2 cm and metabolic progression from an SUVmax of 2.02 to 4.73. Wedge resection and IHC profiles were consistent with a diagnosis of second primary lung adenocarcinoma, and no malignancy was observed in the mediastinal lymph nodes. The patient, whose FFPE tissue NGS revealed a G719A + L861Q co-mutation and PD-L1 0%, was restaged to stage 4A (M1a) with pleural and paratracheal foci on postoperative PET-CT, and osimertinib 80 mg/day was initiated. PET-CT performed at 3 months showed complete resolution of all FDG-enhancing target lesions, demonstrating a complete response. The response is ongoing at 7 months of follow-up, and the only side effect was a grade 1 acneiform rash. Conclusion: This case demonstrates that osimertinib can achieve an early, deep, and sustainable response in patients with a rare G719A/L861Q co-mutation. Prospective evidence is necessary for rare EGFR subtypes.