A pooled analysis of clinical outcome in driver-gene negative non-small cell lung cancer patients with MET overexpression treated with gumarontinib.

IF 4.3 2区医学 Q2 ONCOLOGY Therapeutic Advances in Medical Oncology Pub Date : 2024-07-31 eCollection Date: 2024-01-01 DOI:10.1177/17588359241264730

Yongfeng Yu, Wen Dong, Yanxia Shi, Rong Wu, Qitao Yu, Feng Ye, Chengzhi Zhou, Xiaorong Dong, Xingya Li, Yongsheng Li, Zhen Li, Lin Wu, Yueyin Pan, Hong Shen, Dehua Wu, Zhongyuan Xu, Jinsheng Wu, Nong Xu, Yanru Qin, Aimin Zang, Jingdong Zhang, Jianya Zhou, Xiaotao Zhang, Yanqiu Zhao, Fugen Li, Huizhen Wang, Qi Liu, Zhenyong Han, Jin Li, Shun Lu

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Abstract

Background: MET overexpression represents the most MET aberration in advanced non-small-cell lung cancer (NSCLC). However, except MET exon 14 (METex14) skipping mutation was recognized as a clinical biomarker, the role of MET overexpression as a predictive factor to MET inhibitor is not clear.

Objectives: The purpose of the pooled analysis is to explore the safety and efficiency of gumarontinib, a highly selective oral MET inhibitor, in drive-gene negative NSCLC patients with MET overexpression.

Design and methods: NSCLC patients with MET overexpression [immunohistochemistry (IHC) ⩾3+ as determined by central laboratory] not carrying epidermal growth factor receptor mutation, METex14 skipping mutation or other known drive gene alternations who received Gumarontinib 300 mg QD from two single arm studies were selected and pooled for the analysis. The efficacy [objective response rate (ORR), disease control rate (DCR), duration of response, progression-free survival (PFS) and overall survival (OS)] and safety [treatment emergent adverse event (TEAE), treatment related AE (TRAE) and serious AE (SAE) were assessed.

Results: A total of 32 patients with MET overexpression were included in the analysis, including 12 treatment naïve patients who refused or were unsuitable for chemotherapy, and 20 pre-treated patients who received ⩾1 lines of prior systemic anti-tumour therapies. Overall, the ORR was 37.5% [95% confidence interval (CI): 21.1-56.3%], the DCR was 81.3% (95% CI: 63.6-92.8%), median PFS (mPFS) and median OS (mOS) were 6.9 month (95% CI: 3.6-9.7) and 17.0 month (95% CI: 10.3-not evaluable), respectively. The most common AEs were oedema (59.4%), hypoalbuminaemia (40.6%), alanine aminotransferase increased (31.3%).

Conclusion: Gumarontinib showed promising antitumour activity in driver-gene negative locally advanced or metastatic NSCLC patients with MET overexpression, which warranted a further clinical trial.

Trial registration: ClinicalTrials.gov identifier: NCT03457532; NCT04270591.

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对使用古马隆替尼治疗MET过表达的驱动基因阴性非小细胞肺癌患者临床疗效的汇总分析。

背景：MET过表达是晚期非小细胞肺癌（NSCLC）中最常见的MET畸变。然而，除了MET外显子14（METex14）跳越突变被认为是一种临床生物标志物外，MET过表达作为MET抑制剂预测因素的作用尚不明确：汇总分析的目的是探讨高选择性口服MET抑制剂古马隆替尼在MET过表达的驱动基因阴性NSCLC患者中的安全性和有效性：选取两项单臂研究中接受古马隆替尼 300 毫克 QD 治疗的 MET 过表达 NSCLC 患者（免疫组化 (IHC) ⩾3+，由中心实验室测定），不携带表皮生长因子受体突变、METex14 跳越突变或其他已知的驱动基因变异，并将其汇总进行分析。对疗效[客观反应率（ORR）、疾病控制率（DCR）、反应持续时间、无进展生存期（PFS）和总生存期（OS）]和安全性[治疗突发不良事件（TEAE）、治疗相关不良事件（TRAE）和严重不良事件（SAE）]进行了评估：共有32名MET过表达患者纳入分析，其中包括12名拒绝或不适合化疗的治疗新患者，以及20名接受过⩾1种系统抗肿瘤疗法的预处理患者。总体而言，ORR 为 37.5% [95% 置信区间 (CI)：21.1-56.3%]，DCR 为 81.3%（95% CI：63.6-92.8%），中位 PFS（mPFS）和中位 OS（mOS）分别为 6.9 个月（95% CI：3.6-9.7）和 17.0 个月（95% CI：10.3-无法评估）。最常见的AE为水肿（59.4%）、低白蛋白血症（40.6%）、丙氨酸氨基转移酶升高（31.3%）：古马罗替尼在MET过表达的驱动基因阴性局部晚期或转移性NSCLC患者中显示出良好的抗肿瘤活性，值得进一步开展临床试验：试验注册：ClinicalTrials.gov identifier：NCT03457532；NCT04270591。

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来源期刊

Therapeutic Advances in Medical Oncology ONCOLOGY-

CiteScore

8.20

自引率

2.00%

发文量

160

审稿时长

15 weeks

期刊介绍： Therapeutic Advances in Medical Oncology is an open access, peer-reviewed journal delivering the highest quality articles, reviews, and scholarly comment on pioneering efforts and innovative studies in the medical treatment of cancer. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in medical oncology, providing a forum in print and online for publishing the highest quality articles in this area. This journal is a member of the Committee on Publication Ethics (COPE).