| Summary: | Yan Gao,1 Aihong Zheng,2 Xiuming Zhu,2 Jia Song,3 Qian Xue2 1Department of Western Medicine, Wenxin Community Health Service Center, Hangzhou 310016, China; 2The Department of Medical Oncology, Zhejiang Provincial People’s Hospital, Hangzhou 310014, China; 3The Medical Department, 3D Medicines Inc., Shanghai 201114, China Background: HER2 mutations are identified in approximately 2% of non-small-cell lung cancer (NSCLC) cases and are predominantly observed in non-smokers, females, and adenocarcinoma patients. Although afatinib is recommended for treating NSCLC patients with HER2 mutation, the therapy is most efficacious in patients harboring HER2 exon 20 insertions, especially the in-frame insertion YVMA. Research on the treatment of the extracellular domain mutation is relatively rare.Case presentation: We discuss a 76-year-old Chinese man with a heavy-smoking history who was diagnosed with stage IV squamous cell lung carcinoma. First-line treatment with the angiogenesis inhibitor endostar and systemic chemotherapy with docetaxel plus cisplatin were administered, but the patient ceased treatment because of chemotherapy-induced adverse events. Based on the test result from an amplification refractory mutation system PCR, EGFR-inhibitor icotinib was prescribed, but there was still no evidence of a response. Then, next-generation sequencing identified an HER2 S310Y mutation, and afatinib therapy resulted in a gradual, but substantial reduction in tumor size.Conclusion: This is the first published case report of the successful management of HER2 S310Y mutation squamous cell lung carcinoma with afatinib. Considering the fact that this rare HER2 mutation clinically benefited from afatinib treatment, attention should be paid to the incidence of HER2 in NSCLC patients with inconsistent histological characteristics compared with those previous published. With the guidance of a precise diagnosis, we should realize the significance of other HER2 gene mutations and next-generation sequencing as a diagnostic method. Keywords: afatinib, HER2 S310Y, squamous cell lung carcinoma
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