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Abstract：
UNASSIGNED: Some studies of dual-targeted therapy (DTT) targeting epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET) have shown promising efficacy in non-small-cell lung cancer (NSCLC). Consequently, patient management following DTT resistance has gained significance. However, the underlying resistance mechanisms and clinical outcomes in these patients remain unclear.
UNASSIGNED: This study aimed to delineate the molecular characteristics and survival outcomes of patients with NSCLC harboring EGFR mutations and acquired MET amplification after developing resistance to DTT.
UNASSIGNED: We conducted a retrospective analysis of patients with NSCLC with EGFR mutations and acquired MET amplification who exhibited resistance to EGFR/MET DTT.
UNASSIGNED: Next-generation sequencing (NGS) was performed on patients with available tissue samples before and/or after the development of resistance to DTT. Stratified analyses were carried out based on data sources and subsequent salvage treatments. Univariate/multivariate Cox regression models and survival analyses were employed to explore potential independent prognostic factors.
UNASSIGNED: The study included 77 NSCLC patients, with NGS conducted on 19 patients. We observed many resistance mechanisms, including EGFR-dependent pathways (4/19, 21.1%), MET-dependent pathways (2/19, 10.5%), EGFR/MET co-dependent pathways (2/19, 10.5%), and EGFR/MET-independent resistance mechanisms (11/19, 57.9%). Post-progression progression-free survival (pPFS) and post-progression overall survival (pOS) significantly varied among patients who received the best supportive care (BSC), targeted therapy, or chemotherapy (CT), with median pPFS of 1.5, 3.9, and 4.9 months, respectively (p = 0.003). Median pOS were 2.3, 7.7, and 9.2 months, respectively (p < 0.001). The number of treatment lines following DTT resistance and the Eastern Cooperative Oncology Group performance status emerged as the independent prognostic factors.
UNASSIGNED: This study revealed a heterogeneous landscape of resistance mechanisms to EGFR/MET DTT, with a similar prevalence of on- and off-target mechanisms. Targeted therapy or CT, as compared to BSC, exhibited the potential to improve survival outcomes for patients with advanced NSCLC following resistance to DTT.
UNASSIGNED: This study aimed to delineate the molecular characteristics and survival outcomes of patients with NSCLC harboring EGFR mutations and acquired MET amplification after developing resistance to DTT.
UNASSIGNED: We conducted a retrospective analysis of patients with NSCLC with EGFR mutations and acquired MET amplification who exhibited resistance to EGFR/MET DTT.
UNASSIGNED: Next-generation sequencing (NGS) was performed on patients with available tissue samples before and/or after the development of resistance to DTT. Stratified analyses were carried out based on data sources and subsequent salvage treatments. Univariate/multivariate Cox regression models and survival analyses were employed to explore potential independent prognostic factors.
UNASSIGNED: The study included 77 NSCLC patients, with NGS conducted on 19 patients. We observed many resistance mechanisms, including EGFR-dependent pathways (4/19, 21.1%), MET-dependent pathways (2/19, 10.5%), EGFR/MET co-dependent pathways (2/19, 10.5%), and EGFR/MET-independent resistance mechanisms (11/19, 57.9%). Post-progression progression-free survival (pPFS) and post-progression overall survival (pOS) significantly varied among patients who received the best supportive care (BSC), targeted therapy, or chemotherapy (CT), with median pPFS of 1.5, 3.9, and 4.9 months, respectively (p = 0.003). Median pOS were 2.3, 7.7, and 9.2 months, respectively (p < 0.001). The number of treatment lines following DTT resistance and the Eastern Cooperative Oncology Group performance status emerged as the independent prognostic factors.
UNASSIGNED: This study revealed a heterogeneous landscape of resistance mechanisms to EGFR/MET DTT, with a similar prevalence of on- and off-target mechanisms. Targeted therapy or CT, as compared to BSC, exhibited the potential to improve survival outcomes for patients with advanced NSCLC following resistance to DTT.
摘要：
■针对表皮生长因子受体（EGFR）和间充质上皮转化（MET）的双靶向治疗（DTT）的一些研究在非小细胞肺癌（NSCLC）中显示出有希望的疗效。因此,DTT抵抗后的患者管理具有重要意义。然而,这些患者的潜在耐药机制和临床结局尚不清楚.
■本研究旨在描述携带EGFR突变并在对DTT产生耐药性后获得MET扩增的NSCLC患者的分子特征和生存结果。
■我们对EGFR突变和获得性MET扩增的NSCLC患者进行了回顾性分析，这些患者表现出对EGFR/METDTT的耐药性。
■在对DTT产生耐药性之前和/或之后，对具有可用组织样本的患者进行了下一代测序（NGS）。根据数据源和随后的抢救处理进行分层分析。采用单变量/多变量Cox回归模型和生存分析来探索潜在的独立预后因素。
■该研究包括77位非小细胞肺癌患者，对19名患者进行了NGS。我们观察到许多抗性机制，包括EGFR依赖性通路（4/19，21.1%），MET依赖性途径（2/19，10.5%），EGFR/MET共同依赖途径（2/19，10.5%），和EGFR/MET非依赖性耐药机制（11/19，57.9%）。接受最佳支持治疗（BSC）的患者的进展后无进展生存期（pPFS）和进展后总生存期（pOS）显着不同，靶向治疗,或化疗（CT），pPFS中位数为1.5、3.9和4.9个月，分别(p=0.003)。中位数pOS分别为2.3、7.7和9.2个月，分别(p<0.001)。DTT耐药后的治疗线数量和东部肿瘤协作组的表现状态成为独立的预后因素。
■这项研究揭示了EGFR/METDTT耐药机制的异质性，与类似的流行率的目标和脱靶机制。靶向治疗或CT，与BSC相比，显示出改善DTT耐药后晚期NSCLC患者生存结局的潜力。
■本研究旨在描述携带EGFR突变并在对DTT产生耐药性后获得MET扩增的NSCLC患者的分子特征和生存结果。
■我们对EGFR突变和获得性MET扩增的NSCLC患者进行了回顾性分析，这些患者表现出对EGFR/METDTT的耐药性。
■在对DTT产生耐药性之前和/或之后，对具有可用组织样本的患者进行了下一代测序（NGS）。根据数据源和随后的抢救处理进行分层分析。采用单变量/多变量Cox回归模型和生存分析来探索潜在的独立预后因素。
■该研究包括77位非小细胞肺癌患者，对19名患者进行了NGS。我们观察到许多抗性机制，包括EGFR依赖性通路（4/19，21.1%），MET依赖性途径（2/19，10.5%），EGFR/MET共同依赖途径（2/19，10.5%），和EGFR/MET非依赖性耐药机制（11/19，57.9%）。接受最佳支持治疗（BSC）的患者的进展后无进展生存期（pPFS）和进展后总生存期（pOS）显着不同，靶向治疗,或化疗（CT），pPFS中位数为1.5、3.9和4.9个月，分别(p=0.003)。中位数pOS分别为2.3、7.7和9.2个月，分别(p<0.001)。DTT耐药后的治疗线数量和东部肿瘤协作组的表现状态成为独立的预后因素。
■这项研究揭示了EGFR/METDTT耐药机制的异质性，与类似的流行率的目标和脱靶机制。靶向治疗或CT，与BSC相比，显示出改善DTT耐药后晚期NSCLC患者生存结局的潜力。
