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Multidimensional Coculture System to Model Lung Squamous Carcinoma Progression
Published on: March 17, 2020
Clinical benefit from afatinib in an advanced squamous cell lung carcinoma patient harboring HER2 S310Y mutation: a
Yan Gao1, Aihong Zheng2, Xiuming Zhu2
1Department of Western Medicine, Wenxin Community Health Service Center, Hangzhou 310016, 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.
Insights
Afatinib successfully treated a rare HER2 S310Y mutation in a patient with non-small cell lung cancer (NSCLC). This finding highlights the importance of next-generation sequencing for identifying actionable HER2 mutations in NSCLC.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- HER2 mutations occur in ~2% of non-small cell lung cancer (NSCLC), primarily in non-smokers with adenocarcinoma.
- Afatinib is recommended for HER2-mutated NSCLC, most effective for exon 20 insertions like YVMA.
- Treatment for extracellular domain HER2 mutations remains under-researched.
Observation:
- A 76-year-old male smoker with stage IV squamous cell lung carcinoma received standard chemotherapy and EGFR-inhibitor therapy without response.
- Next-generation sequencing revealed an uncommon HER2 S310Y mutation.
- The patient was subsequently treated with afatinib.
Findings:
- Afatinib treatment led to a significant reduction in tumor size in this patient.
- This is the first reported case of successful afatinib treatment for HER2 S310Y mutated squamous cell lung carcinoma.
- The patient experienced a gradual but substantial decrease in tumor burden.
Implications:
- This case suggests afatinib may be effective for HER2 S310Y mutations in NSCLC.
- It underscores the importance of considering HER2 mutations in NSCLC patients with atypical characteristics.
- Next-generation sequencing is crucial for identifying rare, actionable HER2 mutations.
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