Purpose: HER2  mutations are identified in approximately 2% of non-small-cell lung cancer (NSCLC) cases; however, until now, there are no approved standard targeted therapy for NSCLC patients harboring HER2  mutations.
Case presentation: We present a 63-year-old male with a long smoking history, who was diagnosed with stage IV squamous cell lung cancer. After the failures of two lines of treatment with carboplatin plus gemcitabine and nidaplatin plus docetaxel, in turn, the patient received a next-generation sequencing of circulating tumor DNA to seek for potential treatment opportunities. A HER2  R896G mutation was identified with an allelic fraction of 50.77%. The patient received afatinib 40 mg a day and reached a partial response after two months of treatment. The progression-free survival was more than 14 months and the treatment of afatinib was ongoing. During the treatment, treatment-related paronychia and stomatitis occurred and relieved without any management.
Conclusion: This is the first case report describing a NSCLC patient harboring a rare HER2  R896G mutation who responds to afatinib. This case suggests that afatinib might be efficacious in NSCLC patients harboring HER2  R896G mutations, and these results need to be further studied in prospective clinical trials.
Keywords: afatinib, non-small cell lung cancer, HER2  R896G, next generation sequencing