首页|伏美替尼治疗携带EGFR敏感突变的原发广泛期小细胞肺癌案例表型分析

伏美替尼治疗携带EGFR敏感突变的原发广泛期小细胞肺癌案例表型分析

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目的:探讨伏美替尼治疗携带表皮生长因子受体(epidermal growth factor receptor,EGFR)敏感突变的原发小细胞肺癌(small cell lung cancer,SCLC)的疗效,以及肿瘤基因组、转录组和免疫微环境的特点。方法:分析1例初诊为广泛期的SCLC,基因检测发现了EGFR19外显子缺失突变。患者在一线标准化疗进展后接受了第三代靶向药物伏美替尼治疗,获得疾病缓解,5个月的无进展生存。伏美替尼进展后肺部病灶再次活检,并进一步行基因组、转录组及肿瘤免疫微环境分析。结果:进展后活检再次证实SCLC的组织病理学诊断,基因检测仍然存在EGFR19外显子缺失突变。转录组学分析发现该例患者转录因子亚型符合SCLC-A型。患者治疗前后肿瘤突变负荷、PD-L1 TPS、肿瘤浸润CD4+和CD8+T细胞分布密度均较低,提示抑制性的免疫微环境。结论:携带EGFR敏感突变的广泛期SCLC具有独特的分子表型和肿瘤免疫微环境,伏美替尼可能是这类肿瘤的二线治疗选择之一。
Furmonertinib in the treatment of de novo extensive-stage small cell lung cancer harboring an EGFR sensitive mutation:phenotypic analysis of a case
Objective:We investigated the efficacy of furmonertinib in the treatment of de novo small cell lung cancer (SCLC) carrying epi-dermal growth factor receptor (EGFR) sensitive mutations,and elucidated characteristics of the tumor genome,transcriptome,and immune microenvironment. Methods:We analyzed the case of a female patient initially diagnosed with extensive-stage SCLC who had an exon 19 deletion in her EGFR gene. The patient's disease progressed under first-line standard chemotherapy. She thus received the third-generation EGFR-TKI furmonertinib as her second-line treatment,achieving a partial response (PR) and 5-month progression-free survival. After furmon-ertinib treatment failed,a lung tumor biopsy was performed. Genomic,transcriptomic,and tumor immune microenvironment analyses were performed. Results:The histopathological diagnosis of SCLC was confirmed after progression on furmonertinib. Genetic testing of the treated tumor tissues showed that the patient carried an EGFR exon 19 deletion mutation. Transcriptome analysis revealed that the patient's transcriptional molecular subtype was SCLC-A. The tumor mutational burden,PD-L1 TPS,and density of tumor-infiltrating CD4+and CD8+T cells remained at a low level throughout the course of the disease,suggesting that the immune microenvironment was suppressive. Conclu-sions:Extensive-stage SCLC with EGFR-sensitive mutations exhibits a unique phenotype and tumor immune microenvironment. Furmon-ertinib could be an alternative second-line treatment for this type of tumor entity.

extensive-stage small cell lung cancerEGFR mutationtargeted therapytranscriptional molecular subtypestumor immune microenvironment

蒋湘俐、李咏馨、张江燕、张艳辉、刘圣娥、梁颖、李梦洁、陈鹏

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天津医科大学肿瘤医院肺部肿瘤内科,国家恶性肿瘤临床医学研究中心,天津市肿瘤防治重点实验室,天津市恶性肿瘤临床医学研究中心 天津市300060

南京世和基因检测公司

天津医科大学肿瘤医院病理科

广泛期小细胞肺癌 EGFR突变 靶向治疗 转录因子分型 肿瘤免疫微环境

2024

中国肿瘤临床
中国抗癌协会

中国肿瘤临床

CSTPCD北大核心
影响因子:1.32
ISSN:1000-8179
年,卷(期):2024.51(21)