并发TP53突变促进EGFR外显子20s768i突变型肺腺癌的耐药进化:一例报告和文献综述

IF 0.7 Q4 ONCOLOGY
Case Reports in Oncology Pub Date : 2025-01-09 eCollection Date: 2025-01-01 DOI:10.1159/000543453
Huijuan Zhu, Hui Tang, Huizhen Peng, Wei Ding
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引用次数: 0

摘要

简介:肺腺癌是非小细胞肺癌中最常见的亚型,而表皮生长因子受体(EGFR)突变是癌症(NSCLC)发展中最常见的驱动基因。其中外显子18-21的突变最为常见,尤其是外显子19和21的缺失,其中L858R突变最为常见。其他突变如S768I、G719X和20ins相对罕见。在EGFR突变的肺腺癌患者群体中,可能会发生一些常见的突变,尤其是TP53。病例介绍:本研究回顾分析肺腺癌的新辅助治疗,并复习相关文献。患者被诊断为T4N3M1a, IVa期。化疗860mg培美曲塞和480mg卡铂,免疫治疗200mg辛替单抗1个月后,对常规化疗反应良好,但随访CT扫描显示疾病进展。下一代测序显示EGFR外显子20错义突变(p.S768I和p.V774M)结合肿瘤蛋白p53 (TP53) (p.Y220C)错义突变,突变丰度分别为48.6%/49.7%和49.2%。随后,给予紫杉醇白蛋白400mg化疗和派姆单抗200mg治疗,然后口服阿法替尼靶向治疗(PFS: 12个月)。随后发生脑转移,改用奥西替尼靶向治疗(PFS: 9个月)。治疗效果显著,但由于副作用严重,患者自行停药。5个月后,患者再次病情加重,CEA水平升高。改用福莫那替尼(PFS: 3个月)和顺沃西替尼(PFS: 3个月)靶向治疗。3个月后血CEA水平短暂下降后继续升高,提示病情危重。结论:结果表明,阿法替尼和奥西替尼靶向治疗EGFR S7688I/V774M和TP53突变的PFS优于呋蒙尼替尼和顺沃西替尼靶向治疗。同时,铂类化疗联合免疫治疗可能是NSCLC IVa期患者一种潜在的新辅助治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Concurrent TP53 Mutations Facilitate Resistance Evolution in EGFR Exon 20 S768I Mutant Lung Adenocarcinoma: A Case Report and Review of the Literature.

Introduction: Adenocarcinoma of the lung is the most common subtype of non-small cell lung cancer, and epidermal growth factor receptor (EGFR) mutations are the most common driver genes in the development of cancer (NSCLC). Among them, mutations in exons 18-21 are the most frequent, especially the deletion of exons 19 and 21, where L858R mutations are the most common. Other mutations such as S768I, G719X, and 20ins are relatively rare. In the population of lung adenocarcinoma patients with EGFR mutations, some common mutations may occur, especially TP53.

Case presentation: Here, this study presents a retrospective analysis of neoadjuvant therapy for lung adenocarcinoma and reviews relevant literature. The patient was diagnosed with T4N3M1a, stage IVa. After 1 month of chemotherapy with 860 mg of pemetrexed and 480 mg of carboplatin, and immunotherapy with 200 mg of sintilimab, good response to conventional chemotherapy, but a follow-up CT scan showed disease progression. Next-generation sequencing showed EGFR exon 20 missense mutation (p.S768I and p.V774M) combined with tumor protein p53 (TP53) (p.Y220C) missense mutation, with mutation abundance of 48.6%/49.7% and 49.2%, respectively. Subsequently, chemotherapy with paclitaxel albumin 400 mg and treatment with pembrolizumab 200 mg were administered, followed by targeted treatment with oral afatinib (PFS: 12 months). And then, brain metastasis occurred, and targeted treatment with osimertinib was used instead (PFS: 9 months). The therapeutic effect is significant, but due to severe side effects, the patient stopped taking the medication on their own. Five months later, the patient became seriously ill again and CEA levels increased. Targeted treatment with furmonertinib (PFS: 3 months) and sunvozertinib (PFS: 3 months) was used instead. Three months later, the blood CEA level briefly decreased and then continued to increase, indicating the patient's critical condition.

Conclusion: The results indicate that targeted therapy with afatinib and osimertinib for EGFR S7688I/V774M and TP53 mutations has better PFS than targeted therapy with furmonertinib and sunvozertinib. Simultaneously, the combination of platinum-based chemotherapy and immunotherapy may be a potential neoadjuvant therapy for NSCLC IVa stage patients.

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CiteScore
1.40
自引率
12.50%
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