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阿法替尼治疗携表皮生长因子受体外显子 18 E709_T710delinsD 突变的晚期非小细胞肺癌:一例报告。

Afatinib for the treatment of advanced non-small-cell lung cancer harboring an epidermal growth factor receptor exon 18 E709_T710delinsD mutation: a case report.

机构信息

University Hospital Ghent, Ghent, Belgium.

出版信息

J Med Case Rep. 2021 Nov 22;15(1):562. doi: 10.1186/s13256-021-02994-0.

Abstract

BACKGROUND

The discovery of epidermal growth factor receptor oncogenic driver mutations has changed the therapeutic landscape of advanced non-small cell lung cancer in the past decade. Since the introduction of next-generation sequencing, uncommon epidermal growth factor receptor mutations are more frequently discovered. Because seldom evaluated in clinical trials, their clinical significance and response on tyrosine kinase inhibitors are less well known.

CASE PRESENTATION

A 58-year-old Caucasian woman with no smoking history presented with advanced non-small cell lung cancer. Liver biopsy revealed an adenocarcinoma with a programmed death ligand-1 tumor proportion score of 30% and no common oncogenic driver mutations. A combination of chemotherapy and immunotherapy was started as first-line treatment. However, treatment was ceased after 18 weeks because of immune-related renal failure and disease progression. In the meantime, the next-generation sequencing results of the liver biopsy had revealed an exon 18 E709_T710delinsD mutation. Therefore, afatinib was administered, which was moderately tolerated with grade 2 paronychia and acneiform skin eruption. After 6 months, a partial response with ongoing decrease of the liver metastasis was retained.

CONCLUSION

Because of the lack of clinical trials, tumor heterogeneity, and a tyrosine kinase inhibitor affinity related to the different mutation types, it is difficult to predict the clinical outcome of tyrosine kinase inhibitor in uncommon mutations. Therefore, a therapeutic trial with tyrosine kinase inhibitor has to be considered, but the expected clinical response is lower than for common mutations.

摘要

背景

在过去十年中,表皮生长因子受体致癌驱动突变的发现改变了晚期非小细胞肺癌的治疗格局。自从引入下一代测序以来,罕见的表皮生长因子受体突变越来越频繁地被发现。由于在临床试验中很少评估,它们对酪氨酸激酶抑制剂的临床意义和反应知之甚少。

病例介绍

一名 58 岁的高加索女性,无吸烟史,患有晚期非小细胞肺癌。肝脏活检显示腺癌,程序性死亡配体-1 肿瘤比例评分为 30%,无常见的致癌驱动突变。一线治疗采用化疗和免疫治疗联合。然而,由于免疫相关的肾功能衰竭和疾病进展,治疗在 18 周后停止。与此同时,肝脏活检的下一代测序结果显示存在外显子 18 E709_T710delinsD 突变。因此,给予阿法替尼治疗,其耐受性良好,仅出现 2 级甲周皮炎和痤疮样皮疹。6 个月后,部分缓解,肝转移持续减少。

结论

由于缺乏临床试验、肿瘤异质性以及与不同突变类型相关的酪氨酸激酶抑制剂亲和力,因此很难预测罕见突变的酪氨酸激酶抑制剂的临床疗效。因此,必须考虑使用酪氨酸激酶抑制剂进行治疗,但预期的临床反应低于常见突变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/497a/8609878/6c035e32448b/13256_2021_2994_Fig1_HTML.jpg

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