Abstract：
BACKGROUND: Mesenchymal epithelial transition factor (MET) is a rare oncologic driver gene, and information on immunotherapy for non-small cell lung cancer (NSCLC) patients with this driver gene is limited. Here we evaluate the efficacy and safety of immune checkpoint inhibitors (ICI) under different therapeutic regimen for NSCLC patients with MET alterations.
METHODS: From June 2019 to December 2023, we assessed the efficacy and toxicity of ICIs in 42 NSCLC patients with MET alterations. Survival curves were plotted using the Kaplan-Meier method and the Cox proportional hazards model applied for univariate and multivariate analyses. We assessed the size of target lesion according to RECIST v1.1, and objective response rate (ORR) was defined as the sum of complete response (CR) and partial response (PR), disease control rate (DCR) as the sum of CR, PR, and disease stable.
RESULTS: A total of 42 NSCLC patients with MET alterations were included in this retrospective study, 10 was MET 14 skipping mutation and 32 was MET amplification. The ORR for ICI treatment was 30.95% and the DCR was 71.43%. Median progression-free survival (mPFS) and median overall survival (OS) were 4.40 and 13.97 months, respectively. There exists statistical differences between the mPFS of ICI monotherapy and combine ICI therapy (2.8 vs 7.8 months, p = 0.022). The incidence of drug-related adverse reactions was 47.62%, mainly bone marrow suppression (14.28%), immune-related pneumonia (7.14%), and liver function impairment (7.14%), and six patients (14.28%) experiencing grade 3 or above adverse events.
CONCLUSIONS: NSCLC patients with MET alterations can benefit from immunotherapy, especially the patients treated by combined ICI therapy. However, special attention should be paid to the occurrence of grade 3/4 adverse reactions while using the combined ICI therapy.
METHODS: From June 2019 to December 2023, we assessed the efficacy and toxicity of ICIs in 42 NSCLC patients with MET alterations. Survival curves were plotted using the Kaplan-Meier method and the Cox proportional hazards model applied for univariate and multivariate analyses. We assessed the size of target lesion according to RECIST v1.1, and objective response rate (ORR) was defined as the sum of complete response (CR) and partial response (PR), disease control rate (DCR) as the sum of CR, PR, and disease stable.
RESULTS: A total of 42 NSCLC patients with MET alterations were included in this retrospective study, 10 was MET 14 skipping mutation and 32 was MET amplification. The ORR for ICI treatment was 30.95% and the DCR was 71.43%. Median progression-free survival (mPFS) and median overall survival (OS) were 4.40 and 13.97 months, respectively. There exists statistical differences between the mPFS of ICI monotherapy and combine ICI therapy (2.8 vs 7.8 months, p = 0.022). The incidence of drug-related adverse reactions was 47.62%, mainly bone marrow suppression (14.28%), immune-related pneumonia (7.14%), and liver function impairment (7.14%), and six patients (14.28%) experiencing grade 3 or above adverse events.
CONCLUSIONS: NSCLC patients with MET alterations can benefit from immunotherapy, especially the patients treated by combined ICI therapy. However, special attention should be paid to the occurrence of grade 3/4 adverse reactions while using the combined ICI therapy.
摘要：
背景：间充质上皮转化因子（MET）是一种罕见的肿瘤驱动基因，而对携带该驱动基因的非小细胞肺癌(NSCLC)患者的免疫治疗信息有限.在这里，我们评估了不同治疗方案下免疫检查点抑制剂（ICI）对MET改变的NSCLC患者的疗效和安全性。
方法：从2019年6月至2023年12月，我们评估了ICIs在42例MET改变的NSCLC患者中的疗效和毒性。使用Kaplan-Meier方法绘制生存曲线，并应用Cox比例风险模型进行单变量和多变量分析。我们根据RECISTv1.1评估靶病变的大小，客观反应率（ORR）定义为完全反应（CR）和部分反应（PR）的总和，疾病控制率(DCR)为CR的总和，PR,疾病稳定。
结果：本回顾性研究共纳入42例MET改变的非小细胞肺癌患者，10是MET14跳跃突变,32是MET扩增。ICI治疗的ORR为30.95%,DCR为71.43%。中位无进展生存期（mPFS）和中位总生存期（OS）分别为4.40和13.97个月，分别。ICI单药治疗和联合ICI治疗的mPFS之间存在统计学差异（2.8vs7.8个月，p=0.022)。药物相关不良反应发生率为47.62%,以骨髓抑制为主(14.28%),免疫相关肺炎（7.14%），肝功能损害（7.14%），6例患者（14.28%）出现3级或以上不良事件。
结论：MET改变的NSCLC患者可以从免疫治疗中获益，尤其是ICI联合治疗的患者。然而,在使用联合ICI治疗时应特别注意3/4级不良反应的发生。
方法：从2019年6月至2023年12月，我们评估了ICIs在42例MET改变的NSCLC患者中的疗效和毒性。使用Kaplan-Meier方法绘制生存曲线，并应用Cox比例风险模型进行单变量和多变量分析。我们根据RECISTv1.1评估靶病变的大小，客观反应率（ORR）定义为完全反应（CR）和部分反应（PR）的总和，疾病控制率(DCR)为CR的总和，PR,疾病稳定。
结果：本回顾性研究共纳入42例MET改变的非小细胞肺癌患者，10是MET14跳跃突变,32是MET扩增。ICI治疗的ORR为30.95%,DCR为71.43%。中位无进展生存期（mPFS）和中位总生存期（OS）分别为4.40和13.97个月，分别。ICI单药治疗和联合ICI治疗的mPFS之间存在统计学差异（2.8vs7.8个月，p=0.022)。药物相关不良反应发生率为47.62%,以骨髓抑制为主(14.28%),免疫相关肺炎（7.14%），肝功能损害（7.14%），6例患者（14.28%）出现3级或以上不良事件。
结论：MET改变的NSCLC患者可以从免疫治疗中获益，尤其是ICI联合治疗的患者。然而,在使用联合ICI治疗时应特别注意3/4级不良反应的发生。
