Stage IVB EGFR L861R lung adenocarcinoma treated with afatinib, osimertinib, and chemotherapy

What happened, in summary

This 63-year-old man, a never-smoker with ECOG performance status 0, had an abnormal pulmonary shadow found on routine chest radiography in June 2023. PET/CT showed metastatic disease involving lymph nodes, lung, and bone, and he was diagnosed with cT4N3M1c Stage IVB lung adenocarcinoma. Testing of transbronchial biopsy tissue with the Oncomine Dx Target Test identified an EGFR L861R mutation. Baseline tumor markers were elevated, with CEA 5.5 ng/mL and CYFRA 21-1 5.1 ng/mL. Afatinib 40 mg/day was started. By Day 32, tumor markers had fallen, but grade 1 diarrhea and facial acneiform rash led to dose reduction to 30 mg/day. On Day 49, CT showed shrinkage of the primary lung tumor but also ground-glass opacities and consolidation around the tumor. CEA rose by Day 56, and the opacities did not improve after afatinib was stopped, raising concern for carcinomatous lymphangitis. Because afatinib re-escalation was not feasible, treatment switched to osimertinib 80 mg/day. Tumor markers decreased and the primary tumor stayed stable, but new ground-glass opacities developed. Osimertinib was stopped on Day 112; the opacities resolved and were diagnosed as grade 1 pneumonitis. Later treatment included carboplatin, pemetrexed, bevacizumab, osimertinib rechallenge, and carboplatin plus nab-paclitaxel. As of September 2025, he remained alive 27 months after diagnosis. The pneumonitis question was clinically important because the initial opacities did not improve right away after afatinib stopped, which kept carcinomatous lymphangitis in the differential. Later, after osimertinib was stopped, the opacities resolved and the patient stayed asymptomatic, so the event was assessed as grade 1 drug-induced pneumonitis and managed with observation rather than corticosteroids.