Two cases of non-small cell lung cancer patients with somatic or germline EGFR R776H mutation

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2021-11, Vol.161, p.94-97
• Main Authors: Guo, Tianxing, Zhu, Lihuan, Li, Wujin, Lin, Rongjia, Ding, Yun, Kang, Qiaolin, Shao, Lin, Li, Chanhe, Pan, Xiaojie
• Format: Article
• Language: English
• Subjects: Afatinib; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; EGFR R776H; ErbB Receptors - genetics; Female; Germ Cells; Humans; Lung Neoplasms - diagnosis; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Male; Mutation; Non-small cell lung cancer
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2021.05.036

•Occurrence of germline EGFR R776X mutations is a rare event.•A NSCLC patient harboring EGFR L861Q and R776H responded to afatinib durably.•Germline EGFR R776H is transmittable and may confer to higher susceptibility to lung cancer. The development of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has revolutionized the treatment for non-small cell lung cancer (NSCLC). Comprehensive genomic profiling for NSCLC enables clinicians to identify more uncommon genetic alterations in EGFR. It remains unclear whether patients with certain rare EGFR mutations can benefit from EGFR inhibitors. On the other hand, emerging evidence has also showed the involvement of inherited factors in lung cancer development. However, only few germline EGFR mutations have been reported, and their association with NSCLC familial risk remains ambiguous. Here, we report two cases of NSCLCs with uncommon EGFR mutation R776H. One patient carrying somatic EGFR R776H and L861Q was treated with afatinib and achieved a durable response. The other patient harbored a germline EGFR R776H and her son inherited the same germline R776H mutation whose CT examination showed multiple ground-glass nodules in both lungs requiring further follow-up and diagnosis. Our study demonstrated the responsiveness of compound R776H-L861Q mutations to afatinib. We also revealed the transmission of EGFR R776H and suggested it may confer the high susceptibility to lung cancer.