Histological transformation of lung adenocarcinoma to small cell lung cancer with mutant C797S conferring acquired resistance to osimertinib

• Published in: Journal of international medical research Vol. 48; no. 6; p. 300060520927918
• Main Authors: Ren, Xiaohui, Cai, Xinfeng, Li, Jing, Zhang, Xia, Yu, Jianfei, Song, Xin, Zhang, Henghui, Song, Xia
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-06-2020; Sage Publications Ltd; SAGE Publishing
• Subjects: Acrylamides; Adenocarcinoma of Lung - diagnostic imaging; Adenocarcinoma of Lung - drug therapy; Adenocarcinoma of Lung - genetics; Aniline Compounds; Biopsy; Carcinoma, Non-Small-Cell Lung; Case Report; Chemotherapy; ErbB Receptors - genetics; Humans; Lung cancer; Lung Neoplasms - diagnostic imaging; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Male; Mutation; Neoplasm Recurrence, Local; Protein Kinase Inhibitors - therapeutic use; Small Cell Lung Carcinoma - diagnostic imaging; Small Cell Lung Carcinoma - drug therapy; Small Cell Lung Carcinoma - genetics; Targeted cancer therapy; epidermal growth factor receptor tyrosine kinase inhibitor; histological transformation; lung adenocarcinoma; Osimertinib; C797S; small cell lung carcinoma; acquired resistance
• ISSN: 0300-0605; 1473-2300
• DOI: 10.1177/0300060520927918

Epidermal growth factor receptor (EGFR) gene-mutated non-small cell lung cancer may initially respond to EGFR tyrosine kinase inhibitors (TKIs), but may subsequently become resistant; however, the resistance mechanisms remain unclear. We report a rare case of acquired resistance to osimertinib associated with transformation to small cell lung cancer (SCLC) with cis-C797S mutation. A man with recurrent lung adenocarcinoma harboring an EGFR exon 19 deletion received erlotinib for 10 months following curative surgery and adjuvant chemotherapy. However, he switched to osimertinib after repeat biopsy showed EGFR exon 19 deletion and T790M mutation leading to erlotinib resistance. His disease progressed after 15 months and repeat biopsy showed SCLC. Next-generation sequencing of peripheral blood detected EGFR exon 19 deletion, T790M mutation, cis-C797S mutation, and RB1 inactivation. The tumor was reduced after four cycles of etoposide and cisplatin and his respiratory symptoms improved. However, computed tomography after six cycles of chemotherapy showed multiple bilateral lung lesions, and single-photon emission computed tomography showed bone metastasis. The patient received paclitaxel plus cisplatin for two cycles with partial response. Because heterogeneous genetic and phenotypic mechanisms of TKI-resistance may occur at different times and locations, histopathological and molecular testing both provide evidence to support appropriate treatment.