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.

Conclusion

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.

中文翻译：

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免疫治疗对MET改变的非小细胞肺癌患者的疗效和安全性分析

背景

间充质上皮转化因子（MET）是一种罕见的肿瘤驱动基因，有关具有该驱动基因的非小细胞肺癌（NSCLC）患者免疫治疗的信息有限。在此，我们评估免疫检查点抑制剂（ICI）在不同治疗方案下对具有 MET 改变的 NSCLC 患者的疗效和安全性。

方法

从 2019 年 6 月到 2023 年 12 月，我们评估了 42 名 MET 改变的 NSCLC 患者中 ICI 的疗效和毒性。使用 Kaplan-Meier 方法和用于单变量和多变量分析的 Cox 比例风险模型绘制生存曲线。我们根据RECIST v1.1评估靶病灶的大小，客观缓解率（ORR）定义为完全缓解（CR）和部分缓解（PR）之和，疾病控制率（DCR）定义为CR之和、PR 且疾病稳定。

结果

本回顾性研究共纳入 42 例 MET 改变的 NSCLC 患者，其中 10 例为 MET 14 跳跃突变，32 例为 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 个月和 13.97 个月。 ICI单药治疗和联合ICI治疗的mPFS之间存在统计学差异（2.8个月与7.8个月，p  = 0.022）。药物相关不良反应发生率为47.62%，主要为骨髓抑制（14.28%）、免疫相关性肺炎（7.14%）、肝功能损害（7.14%），3级以上不良反应6例（14.28%）。上述不良事件。

结论

具有 MET 改变的 NSCLC 患者可以从免疫治疗中受益，尤其是联合 ICI 治疗的患者。但联合ICI治疗时应特别注意3/4级不良反应的发生。