EP1.14-35 Squamous Cell Carcinoma Transformation After Acquired Resistance to Osimertinib

Osimertinib is a third-generation epidermal growth factor receptor - tyrosine kinase inhibitor (EGFR-TKI) for the management of NSCLC carrying EGFR T790M mutation after acquired resistance to prior EGFR-TKI and is now the preferred therapy in the front-line. The resistance mechanism of osimertinib, including histologic transformation had been reported, mostly small cell carcinoma. Here we a patient with lung adenocarcinoma with uncommon EGFR H835L +L833V + T790M mutation who developed progressive lung atelectasis after acquired resistance to osimertinib. Bronchoscopic biopsy over the endobronchial tumor was done and the pathology report showed squamous cell carcinoma. Mutation analysis of the squamous cell carcinoma performed by next generation sequencing (FoundationOne® CDx) was performed and reveled complex genomic alteration including EGFR H835L, L833V and T790M mutation, TP53 mutation and mTOR amplification. Squamous cell transformation after acquired resistance to osimeritinib was diagnosed. Then the patient was treated with a mTOR inhibitor, everolimus (5mg /day) plus osimertinib. One month after treatment an initial tumor response was observed, however, a progression occurred after 3 months of treatment. Squamous cell transformation is a rare manifestation of osimertinib resistance, further research is need to investigate the underlying mechanism of this histologic change and discover the proper treatment strategy.