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卡马替尼治疗 MET 外显子 14 跳跃突变或基因扩增的晚期非小细胞肺癌的临床影响。

The Clinical Impact of Capmatinib in the Treatment of Advanced Non-Small Cell Lung Cancer with MET Exon 14 Skipping Mutation or Gene Amplification.

机构信息

Center for Clinical Trials, National Cancer Center, Goyang, Korea.

Department of Pathology, National Cancer Center, Goyang, Korea.

出版信息

Cancer Res Treat. 2021 Oct;53(4):1024-1032. doi: 10.4143/crt.2020.1331. Epub 2021 Jan 29.

Abstract

PURPOSE

Capmatinib, an oral MET kinase inhibitor, has demonstrated its efficacy against non-small cell lung cancer (NSCLC) with MET dysregulation. We investigated its clinical impact in advanced NSCLC with MET exon 14 skipping mutation (METex14) or gene amplification.

MATERIALS AND METHODS

Patients who participated in the screening of a phase II study of capmatinib for advanced NSCLC were enrolled in this study. MET gene copy number (GCN), protein expression, and METex14 were analyzed and the patients' clinical outcome were retrospectively reviewed.

RESULTS

A total of 72 patients were included in this analysis (group A: GCN ≥ 10 or METex14, n=14; group B: others, n=58). Among them, 13 patients were treated with capmatinib (group A, n=8; group B, n=5), and the overall response rate was 50% for group A, and 0% for group B. In all patients, the median overall survival (OS) was 20.2 months (95% confidence interval [CI], 6.9 to not applicable [NA]) for group A, and 11.3 months (95% CI, 8.2 to 20.3) for group B (p=0.457). However, within group A, median OS was 21.5 months (95% CI, 20.8 to NA) for capmatinib-treated, and 7.5 months (95% CI, 3.2 to NA) for capmatinib-untreated patients (p=0.025). Among all capmatinib-untreated patients (n=59), group A showed a trend towards worse OS to group B (median OS, 7.5 months vs. 11.3 months; p=0.123).

CONCLUSION

Our data suggest that capmatinib is a new compelling treatment for NSCLC with MET GCN ≥ 10 or METex14 based on the improved survival within these patients.

摘要

目的

口服 MET 激酶抑制剂卡马替尼在 MET 失调的非小细胞肺癌(NSCLC)中显示出疗效。我们研究了其在 MET 外显子 14 跳跃突变(METex14)或基因扩增的晚期 NSCLC 中的临床影响。

材料和方法

参与卡马替尼治疗晚期 NSCLC 的 II 期研究筛选的患者被纳入本研究。分析了 MET 基因拷贝数(GCN)、蛋白表达和 METex14,并回顾性分析了患者的临床结局。

结果

本分析共纳入 72 例患者(A 组:GCN≥10 或 METex14,n=14;B 组:其他,n=58)。其中,13 例患者接受了卡马替尼治疗(A 组,n=8;B 组,n=5),A 组的总体缓解率为 50%,B 组为 0%。在所有患者中,A 组的中位总生存期(OS)为 20.2 个月(95%置信区间[CI],6.9 至无法评估[NA]),B 组为 11.3 个月(95%CI,8.2 至 20.3)(p=0.457)。然而,在 A 组中,卡马替尼治疗患者的中位 OS 为 21.5 个月(95%CI,20.8 至 NA),卡马替尼未治疗患者的中位 OS 为 7.5 个月(95%CI,3.2 至 NA)(p=0.025)。在所有卡马替尼未治疗患者(n=59)中,A 组的 OS 较 B 组更差(中位 OS,7.5 个月 vs. 11.3 个月;p=0.123)。

结论

我们的数据表明,卡马替尼是一种新的有吸引力的治疗方法,适用于 MET GCN≥10 或 METex14 的 NSCLC,基于这些患者的生存改善。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47e5/8524022/7e0dadddaf98/crt-2020-1331f1.jpg

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