对接受古玛罗替尼治疗的MET过表达驱动基因阴性非小细胞肺癌患者临床结局的汇总分析。
A pooled analysis of clinical outcome in driver-gene negative non-small cell lung cancer patients with MET overexpression treated with gumarontinib.
作者信息
Yu Yongfeng, Dong Wen, Shi Yanxia, Wu Rong, Yu Qitao, Ye Feng, Zhou Chengzhi, Dong Xiaorong, Li Xingya, Li Yongsheng, Li Zhen, Wu Lin, Pan Yueyin, Shen Hong, Wu Dehua, Xu Zhongyuan, Wu Jinsheng, Xu Nong, Qin Yanru, Zang Aimin, Zhang Jingdong, Zhou Jianya, Zhang Xiaotao, Zhao Yanqiu, Li Fugen, Wang Huizhen, Liu Qi, Han Zhenyong, Li Jin, Lu Shun
机构信息
Department of Medical Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Respiratory Medicine, Hainan Cancer Hospital, Haikou, China.
出版信息
Ther Adv Med Oncol. 2024 Jul 31;16:17588359241264730. doi: 10.1177/17588359241264730. eCollection 2024.
BACKGROUND
MET overexpression represents the most aberration in advanced non-small-cell lung cancer (NSCLC). However, except exon 14 (ex14) 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, ex14 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.
背景
MET过表达是晚期非小细胞肺癌（NSCLC）中最常见的异常情况。然而，除了外显子14（ex14）跳跃突变被认为是一种临床生物标志物外，MET过表达作为MET抑制剂预测因子的作用尚不清楚。
目的
汇总分析的目的是探讨高选择性口服MET抑制剂谷美替尼在MET过表达的驱动基因阴性NSCLC患者中的安全性和有效性。
设计与方法
选择两项单臂研究中接受谷美替尼300mg每日一次治疗、MET过表达[经中心实验室确定免疫组化（IHC）≥3+]、未携带表皮生长因子受体突变、ex14跳跃突变或其他已知驱动基因改变的NSCLC患者，并将其汇总进行分析。评估疗效[客观缓解率（ORR）、疾病控制率（DCR）、缓解持续时间、无进展生存期（PFS）和总生存期（OS）]和安全性[治疗期间出现的不良事件（TEAE）、治疗相关不良事件（TRAE）和严重不良事件（SAE）]。
结果
共有32例MET过表达患者纳入分析，其中包括12例初治患者，这些患者拒绝或不适合化疗，以及20例接受过≥1线全身抗肿瘤治疗的经治患者。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-不可评估）。最常见的不良事件为水肿（59.4%）、低白蛋白血症（40.6%）、谷丙转氨酶升高（31.3%）。
结论
谷美替尼在MET过表达的驱动基因阴性局部晚期或转移性NSCLC患者中显示出有前景的抗肿瘤活性，值得进一步开展临床试验。
试验注册
ClinicalTrials.gov标识符：NCT03457532；NCT04270591。
Zotero 插件