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
{"title":"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。","authors":"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","doi":"10.1177/17588359241264730","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>MET overexpression represents the most <i>MET</i> aberration in advanced non-small-cell lung cancer (NSCLC). However, except <i>MET</i> exon 14 (<i>MET</i>ex14) skipping mutation was recognized as a clinical biomarker, the role of MET overexpression as a predictive factor to MET inhibitor is not clear.</p><p><strong>Objectives: </strong>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.</p><p><strong>Design and methods: </strong>NSCLC patients with MET overexpression [immunohistochemistry (IHC) ⩾3+ as determined by central laboratory] not carrying epidermal growth factor receptor mutation, <i>MET</i>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.</p><p><strong>Results: </strong>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%).</p><p><strong>Conclusion: </strong>Gumarontinib showed promising antitumour activity in driver-gene negative locally advanced or metastatic NSCLC patients with MET overexpression, which warranted a further clinical trial.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT03457532; NCT04270591.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241264730"},"PeriodicalIF":4.3000,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11292687/pdf/","citationCount":"0","resultStr":"{\"title\":\"A pooled analysis of clinical outcome in driver-gene negative non-small cell lung cancer patients with MET overexpression treated with gumarontinib.\",\"authors\":\"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\",\"doi\":\"10.1177/17588359241264730\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>MET overexpression represents the most <i>MET</i> aberration in advanced non-small-cell lung cancer (NSCLC). However, except <i>MET</i> exon 14 (<i>MET</i>ex14) skipping mutation was recognized as a clinical biomarker, the role of MET overexpression as a predictive factor to MET inhibitor is not clear.</p><p><strong>Objectives: </strong>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.</p><p><strong>Design and methods: </strong>NSCLC patients with MET overexpression [immunohistochemistry (IHC) ⩾3+ as determined by central laboratory] not carrying epidermal growth factor receptor mutation, <i>MET</i>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.</p><p><strong>Results: </strong>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%).</p><p><strong>Conclusion: </strong>Gumarontinib showed promising antitumour activity in driver-gene negative locally advanced or metastatic NSCLC patients with MET overexpression, which warranted a further clinical trial.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT03457532; NCT04270591.</p>\",\"PeriodicalId\":23053,\"journal\":{\"name\":\"Therapeutic Advances in Medical Oncology\",\"volume\":\"16 \",\"pages\":\"17588359241264730\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-07-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11292687/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Therapeutic Advances in Medical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/17588359241264730\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Advances in Medical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17588359241264730","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
A pooled analysis of clinical outcome in driver-gene negative non-small cell lung cancer patients with MET overexpression treated with gumarontinib.
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.
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).
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