■MET过表达代表了晚期非小细胞肺癌(NSCLC)中MET畸变的最多。然而,除了MET外显子14(METex14)跳跃突变被认为是临床生物标志物,MET过表达作为MET抑制剂预测因子的作用尚不清楚.
■汇总分析的目的是探索gumarontinib的安全性和有效性,一种高度选择性的口服MET抑制剂,在驱动基因阴性的NSCLC患者中,MET过表达。
■NSCLC患者MET过表达[免疫组织化学(IHC)3+由中心实验室确定]不携带表皮生长因子受体突变,选择来自两个单臂研究的接受Gumarontinib300mgQD的METex14跳跃突变或其他已知驱动基因改变并汇集用于分析。疗效[客观反应率(ORR),疾病控制率(DCR),响应的持续时间,无进展生存期(PFS)和总生存期(OS)]和安全性[治疗紧急不良事件(TEAE),评估与治疗相关的AE(TRAE)和严重AE(SAE)。
■共有32例MET过表达患者纳入分析,包括12名拒绝或不适合化疗的未接受治疗的患者,和20名预先治疗的患者谁接受了1行先前的全身抗肿瘤治疗。总的来说,ORR为37.5%[95%置信区间(CI):21.1-56.3%],DCR为81.3%(95%CI:63.6-92.8%),中位数PFS(mPFS)和中位数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),分别。最常见的不良事件是水肿(59.4%),低白蛋白血症(40.6%),丙氨酸转氨酶增加(31.3%)。
■Gumarontinib在MET过表达驱动基因阴性的局部晚期或转移性NSCLC患者中显示出有希望的抗肿瘤活性,这需要进一步的临床试验。
■ClinicalTrials.gov标识符:NCT03457532;NCT04270591。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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%).
UNASSIGNED: Gumarontinib showed promising antitumour activity in driver-gene negative locally advanced or metastatic NSCLC patients with MET overexpression, which warranted a further clinical trial.
UNASSIGNED: ClinicalTrials.gov identifier: NCT03457532; NCT04270591.