吡咯替尼治疗罕见HER2 R456C突变的非小细胞肺癌:一例报告

IF 2.3 4区 医学 Q3 ONCOLOGY
Yajie Wang, Jiaqi Hu, Runze Liu, Pei Li, Luokun Wang, Guangjian Yang
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引用次数: 0

摘要

背景:在非小细胞肺癌(NSCLC)中,HER2外显子20插入对化疗和共价HER2靶向酪氨酸激酶抑制剂(TKIs)表现出相对耐药性。此外,HER2蛋白胞外区域的特异性错义突变已被确定为NSCLC的致癌驱动因素。然而,它们的结构特性和对her2靶向抑制剂的临床反应仍然知之甚少,需要进一步研究。R456C是HER2细胞外结构域罕见的外显子12错义突变,在非小细胞肺癌中文献有限。病例介绍:本研究报告了一例HER2 R456C突变的非典型NSCLC病例,患者在HER2靶向抑制剂pyrotinib的治疗下获得了良好的反应和可观的生存期。患者,65岁男性,诊断为IIIB期肺腺癌,最初接受根治性同步放化疗。在疾病复发时,聚合酶链反应试验未检测到致癌改变,程序性细胞死亡配体1 (PD-L1)表达为阴性。化疗联合贝伐单抗导致疾病稳定,提供6个月的无进展生存期(PFS)获益。然而,安洛替尼被证明对脑转移无效,需要进行脑放疗。随后的肺活检证实为腺癌,下一代测序鉴定出体细胞HER2外显子12错义突变p.R456C。在给予吡罗替尼后,患者的肺转移明显减少,脑转移消退,导致部分缓解和13个月的PFS获益。结论:据我们所知,这项研究是第一个报道的病例,证明了pyrotinib在her2改变的携带ra-re外显子12 R456C突变的NSCLC中有希望的疗效。HER2细胞外片段(如R456C)的异质性改变可能是可靶向的,并且可以通过HER2靶向抑制剂获得生存益处。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Promising Response to Pyrotinib in Non-Small-Cell Lung Cancer with the Rare HER2 R456C Mutation: A Case Report.

Background: HER2 exon 20 insertions exhibit relative resistance to chemotherapy and covalent HER2-targeted tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC). Furthermore, specific missense mutations in the extracellular domain of the HER2 protein have been identified as oncogenic drivers in NSCLC. However, their structural properties and clinical response to HER2-targeted inhibitors remain poorly understood, warranting further investigation. R456C represents a rare exon 12 missense mutation in the HER2 extracellular domain, with limited documentation in NSCLC.

Case presentation: This study presents an atypical case of NSCLC with a HER2 R456C mutation, where the patient experienced a favorable response and substantial survival benefit from the HER2-targeted inhibitor pyrotinib. A patient, a 65-year-old man diagnosed with stage IIIB lung adenocarcinoma, initially underwent radical concurrent chemoradiotherapy. Upon disease recurrence, polymerase chain reaction assay detected no oncogenic alterations, and programmed cell death ligand 1 (PD-L1) expression was negative. Chemotherapy in combination with bevacizumab resulted in stable disease, providing a progression-free survival (PFS) benefit of 6 months. However, anlotinib proved ineffective against brain metastasis, necessitating brain radiotherapy. A subsequent lung biopsy confirmed adenocarcinoma and next-generation sequencing identified a somatic HER2 exon 12 missense mutation, p.R456C. Following pyrotinib administration, the patient's pulmonary metastases significantly diminished, and the brain metastasis regressed, resulting in a partial response and a PFS benefit of 13 months.

Conclusion: To the best of our knowledge, this study represents the first reported case demonstrating the promising efficacy of pyrotinib in HER2-altered NSCLC harboring the ra-re exon 12 R456C mutation. Heterogeneous alterations in the HER2 extracellular segment, such as R456C, may be targetable and could confer survival benefits with HER2-targeted inhibitors.

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来源期刊
Current cancer drug targets
Current cancer drug targets 医学-肿瘤学
CiteScore
5.40
自引率
0.00%
发文量
105
审稿时长
1 months
期刊介绍: Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes. Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer. As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.
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