Efficacy and safety analysis of immunotherapy in non-small cell lung cancer patients with MET alterations

Yanhua Wang, Jingwen Wei, Manyi Xu, Jing Xiang, Keda Shao, Yue Hao, Zhengbo Song
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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.

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.

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免疫疗法对MET改变的非小细胞肺癌患者的疗效和安全性分析
背景间充质上皮细胞转化因子(MET)是一种罕见的肿瘤驱动基因,而针对具有该驱动基因的非小细胞肺癌(NSCLC)患者的免疫疗法信息十分有限。在此,我们评估了免疫检查点抑制剂(ICI)在不同治疗方案下对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例MET改变的NSCLC患者中ICIs的疗效和毒性。采用 Kaplan-Meier 法绘制生存曲线,并应用 Cox 比例危险模型进行单变量和多变量分析。我们根据RECIST v1.1标准评估了靶病灶的大小,客观反应率(ORR)定义为完全反应(CR)和部分反应(PR)之和,疾病控制率(DCR)定义为CR、PR和疾病稳定之和。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 存在统计学差异(2.8 个月 vs 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%)、免疫相关肺炎(7.14%)和肝功能损害(7.14%),6例患者(14.28%)出现3级或以上不良反应。结论MET改变的NSCLC患者可以从免疫疗法中获益,尤其是采用联合ICI疗法的患者,但是在使用联合ICI疗法时应特别注意3/4级不良反应的发生。
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