Stage IV EGFR-mutated lung adenocarcinoma: high-dose furmonertinib after CNS progression

What happened, in summary

This 56-year-old Chinese woman was diagnosed in August 2022 with Stage IV lung adenocarcinoma. CT showed a 4.3 × 4.9 cm mass in the left upper lung with obstructive pneumonia and suspected left hilar lymph-node enlargement. Biopsy of a left supraclavicular lymph node confirmed metastatic non-small-cell carcinoma with adenocarcinoma features. Initial PCR/ARMS testing found an EGFR exon 21 L858R mutation. Brain MRI showed meningeal thickening consistent with metastatic involvement, and PET/CT showed bilateral pleural involvement, carcinomatous lymphangitis, mediastinal and hilar nodal metastases, and multiple bone metastases. She started icotinib in September 2022 and had a partial response by November, although meningeal metastases persisted. In January 2023, she switched to furmonertinib 80 mg daily, later increased to 120 mg for worsening headache and nausea. By November 2023, mediastinal and hilar nodes had enlarged, and the overall response was progressive disease. She then received bevacizumab, pemetrexed, carboplatin, and cranial radiotherapy, but radiotherapy stopped after 9 sessions because of confusion and limb convulsions. Plasma NGS later detected an EGFR exon 14 p.S553Y missense variation. Furmonertinib was restarted at 160 mg/day in late November 2023, then increased to 200 mg/day after new small brain lesions in April 2024 and 240 mg/day after further CNS progression in June 2024. The lung lesion stayed stable to slightly smaller, but CNS disease remained the key setback. Visual complications also became serious: cataracts were suspected first, then optic nerve damage progressed to complete blindness, while CEA initially fell and later rose again with progression.