Squamous cell carcinoma transformation after acquired resistance to osimertinib in a patient with lung adenocarcinoma harboring uncommon EGFR mutation

摘要

A 54-year-old female never smoker, who underwent sur- gery for lung adenocarcinoma (pT2N0M0, stage IB), pre- sented with recurrent lung tumor in sixteen months later. She received several lines of treatment including gefitinib, pemetrexed, erlotinib and then vinorelbine. Due to pro- gressive lung metastasis, she received percutaneous CT- guided re-biopsy and EGFR mutation assay showed H835L t L833V and T790M mutations. Then, she received osimertinib after afatinib failure, and had a response that lasted for 19 months. Dyspnea developed while osimertnib resistance and chest CT scan showed progressive right lower lung collapse and pleural effusion. Bronchoscopy revealed tumor eruption at the proximal right intermedi- ate bronchus, causing lumen narrowing. Biopsy revealed lung tissue with squamous cell carcinoma (SCC), composed of sheets and clusters of dysplastic squamous cells. The tumor cells were immunoreactive for p40 and non-reactive for TTF-1 (Supplementary Fig. 1). Programmed death ligand 1 staining of the tumor by 22C3 showed a 0% tumor proportion score. She received pembrolizumab plus paclitaxel for one month with clinical deterioration. Mu- tation analysis of the squamous cell carcinoma performed by next generation sequencing (FoundationOne? CDx) showed complex genomic alteration including EGFR H835L t L833V and T790M mutations, TP53 mutation and mTOR amplification (Fig. 1A). After discussion with the patient, she received everolimus 5 mg QD for 2 weeks, and osimertinib 80 mg was added (Fig. 1B). CT scan of the chest one month later showed regression of the endo- bronchial tumor and re-expansion of the lung (Fig. 1C). However, progression occurred in the liver and bone after 3 months of treatment.