Characterization of Patients with EGFR Mutation-Positive NSCLC Following Emergence of the Osimertinib Resistance Mutations, L718Q or G724S: A Multicenter Retrospective Observational Study in France

IF 2.7 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY OncoTargets and therapy Pub Date : 2024-05-29 DOI:10.2147/ott.s448909

Mateo Sanchis-Borja, Florian Guisier, Aurélie Swalduz, Hubert Curcio, Victor Basse, Christophe Maritaz, Christos Chouaid, Jean-Bernard Auliac

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Abstract

Purpose: The third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), osimertinib, is an effective first-line therapy for patients with common EGFR mutation-positive non-small cell lung cancer (NSCLC). However, almost all patients become resistant to treatment. In some patients, emergence of tertiary EGFR mutations is implicated as a resistance mechanism. This study describes patients with NSCLC who acquired the rare EGFR mutations, L718Q or G724S, following EGFR TKI treatment.
Patients and Methods: This was a retrospective, observational study undertaken in France from Feb–Nov 2021, in patients with EGFR mutation-positive NSCLC with an acquired L718Q or G724S mutation. Primary objectives were description of tumor characteristics, progression, and progression under treatment.
Results: Nine eligible patients were identified. Acquired resistance to initial EGFR TKI treatment was associated with T790M emergence in six patients, who then received osimertinib monotherapy. Overall, eight patients received osimertinib monotherapy treatment at some point (average treatment duration: 18.3 months). Following the emergence of L718Q or G724S, patients received chemotherapy (n = 4; two of whom subsequently received afatinib), nivolumab (n = 2), afatinib (n = 2), or immunochemotherapy (n = 1). In the four patients who received afatinib after identification of L718Q or G724S, 2 achieved a partial response, one had stable disease and one had progressive disease. Treatment duration was 1.6– 31.7 months. In patients with controlled disease (n = 3), progression-free survival was 6.1– 31.7 months. Two of these patients had previously received osimertinib.
Conclusion: Currently, there is no consensus regarding the treatment of EGFR mutation-positive NSCLC following emergence of the osimertinib resistance mutations, L718Q or G724S. Afatinib appears to be a promising treatment option in this setting.

Keywords: osimertinib, afatinib, real-world evidence, tertiary EGFR mutations

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奥希替尼耐药突变 L718Q 或 G724S 出现后表皮生长因子受体突变阳性 NSCLC 患者的特征：法国一项多中心回顾性观察研究

目的：第三代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）奥西莫替尼是治疗常见EGFR突变阳性非小细胞肺癌（NSCLC）患者的有效一线疗法。然而，几乎所有患者都会对治疗产生耐药性。在一些患者中，表皮生长因子受体三级突变的出现被认为是一种耐药机制。本研究描述了在接受表皮生长因子受体 TKI 治疗后获得罕见表皮生长因子受体突变 L718Q 或 G724S 的 NSCLC 患者：这是一项回顾性观察研究，于2021年2月至11月在法国进行，研究对象为获得L718Q或G724S突变的表皮生长因子受体突变阳性NSCLC患者。研究的主要目的是描述肿瘤特征、病情进展和治疗进展：结果：确定了九名符合条件的患者。6名患者对最初的表皮生长因子受体TKI治疗获得性耐药与T790M的出现有关，这些患者随后接受了奥希替尼单药治疗。总体而言，八名患者在某一阶段接受了奥希替尼单药治疗（平均治疗时间：18.3个月）。出现L718Q或G724S后，患者接受了化疗（4例；其中2例随后接受了阿法替尼治疗）、nivolumab（2例）、阿法替尼（2例）或免疫化疗（1例）。在确定L718Q或G724S后接受阿法替尼治疗的4名患者中，2人获得部分应答，1人病情稳定，1人病情进展。治疗持续时间为 1.6-31.7 个月。在病情得到控制的患者中（n = 3），无进展生存期为 6.1-31.7 个月。其中两名患者曾接受过奥希替尼治疗：目前，对于出现奥希替尼耐药突变（L718Q或G724S）后如何治疗表皮生长因子受体突变阳性的NSCLC尚未达成共识。在这种情况下，阿法替尼似乎是一种很有前景的治疗选择。关键词：奥西美替尼；阿法替尼；真实世界证据；EGFR三级突变

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来源期刊

OncoTargets and therapy BIOTECHNOLOGY & APPLIED MICROBIOLOGY-ONCOLOGY

CiteScore

9.70

自引率

0.00%

发文量

221

审稿时长

1 months

期刊介绍： OncoTargets and Therapy is an international, peer-reviewed journal focusing on molecular aspects of cancer research, that is, the molecular diagnosis of and targeted molecular or precision therapy for all types of cancer. The journal is characterized by the rapid reporting of high-quality original research, basic science, reviews and evaluations, expert opinion and commentary that shed novel insight on a cancer or cancer subtype. Specific topics covered by the journal include: -Novel therapeutic targets and innovative agents -Novel therapeutic regimens for improved benefit and/or decreased side effects -Early stage clinical trials Further considerations when submitting to OncoTargets and Therapy: -Studies containing in vivo animal model data will be considered favorably. -Tissue microarray analyses will not be considered except in cases where they are supported by comprehensive biological studies involving multiple cell lines. -Biomarker association studies will be considered only when validated by comprehensive in vitro data and analysis of human tissue samples. -Studies utilizing publicly available data (e.g. GWAS/TCGA/GEO etc.) should add to the body of knowledge about a specific disease or relevant phenotype and must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Bioinformatics studies must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Single nucleotide polymorphism (SNP) studies will not be considered.