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[阿美替尼治疗EGFR/MET基因异常的非小细胞肺癌患者的疗效和安全性分析:单中心经验]

[Analysis of the Effcacy and Safety of Amivantamab in Non-small Cell Lung Cancer 
Patients with EGFR/MET Gene Abnormalities: A Single Center's Experience].

作者信息

Wang Jingjing, Chi Yujia, Chen Hanxiao, Jia Bo, Zhai Xiaoyu, Ma Menglei, Li Jianjie, Zhuo Minglei

机构信息

Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), 
Department of Thoracic Medical Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.

出版信息

Zhongguo Fei Ai Za Zhi. 2022 Jul 20;25(7):493-500. doi: 10.3779/j.issn.1009-3419.2022.102.26.

Abstract

BACKGROUND

Epidermal growth factor receptor (EGFR) and cellular-mesenchymal to epithelial transition factor (c-Met) are widely expressed on cancer cells. There is a synergistic effect of EGFR and HGF/c-Met pathways on proliferation, downstream activation of signal transduction and an additive effect. Studies show that combination of both signaling pathways could potentially be targeted in a synergistic fashion. Amivantamab, a bispecific monoclonal antibody targeting EGFR and c-Met, yielded robust and durable responses in a variety of clinicals trials. However, few researches have reported its efficacy in Chinese non-small cell lung cancer (NSCLC) patients. This study was conducted to evaluate the effectiveness and tolerance of Amivantamab in NSCLC patients with EGFR/MET gene abnormalities at Peking University Cancer Hospital.

METHODS

The study enrolled NSCLC patients who received Amivantamab in our hospital between August 2020 and December 2021, and analyzed the response, survival, and treatment-related adverse events.

RESULTS

Fifteen patients were enrolled in this research, and six of them received Amivantamab treatment and the other nine patients received Amivantamab plus Lazertinib treatment. The rates of partial response (PR), stable disease (SD), and progressive disease (PD) were 46.7% (7/15), 46.7% (7/15) and 6.7% (1/15), respectively. The overall response rate (ORR) and disease control rate (DCR) were 28.6% (2/7) and 100.0% (7/7) in seven patients with EGFR exon 20 insertion, respectively. The ORR and DCR were 40.0% (2/5) and 100.0% (5/5) in five post-osimertinib EGFR-mutant patients, respectively. After a median follow-up of 8.7 months, the median progression-free survival and overall survival were not reached. The most common treatment-related adverse events were rash (86.7%), paronychia (80.0%), and infusion-related reactions (60.0%), and most of them were graded as 1 to 2. Grade 3 to 4 adverse events included rash (33.3%), alanine aminotransferase elevation (13.3%), gamma-glutamyl transpeptidase elevation (13.3%), peripheral edema (6.7%), thromboembolism (6.7%), interstitial lung disease (6.7%), and thrombocytopenia (6.7%).

CONCLUSIONS

Amivantamab was effective in Chinese NSCLC patients with EGFR exon 20 insertion and post-Osimertinib EGFR-mutant patients, similar to the results of clinical trials conducted in western countries. Amivantamab was well tolerated and emphases should be put on adverse events such as rash, paronychia, and infusion-related reactions.

摘要

背景

表皮生长因子受体(EGFR)和细胞间充质向上皮转化因子(c-Met)在癌细胞上广泛表达。EGFR和HGF/c-Met信号通路在增殖、信号转导下游激活方面存在协同作用以及相加效应。研究表明,这两条信号通路的联合有可能以协同方式作为靶点。阿米万他单抗是一种靶向EGFR和c-Met的双特异性单克隆抗体,在多项临床试验中产生了强劲且持久的反应。然而,很少有研究报道其在中国非小细胞肺癌(NSCLC)患者中的疗效。本研究旨在评估北京大学肿瘤医院中阿米万他单抗在伴有EGFR/MET基因异常的NSCLC患者中的有效性和耐受性。

方法

本研究纳入了2020年8月至2021年12月期间在我院接受阿米万他单抗治疗的NSCLC患者,并分析其反应、生存情况及治疗相关不良事件。

结果

本研究共纳入15例患者,其中6例接受阿米万他单抗单药治疗,另外9例接受阿米万他单抗联合拉泽替尼治疗。部分缓解(PR)、疾病稳定(SD)和疾病进展(PD)的发生率分别为46.7%(7/15)、46.7%(7/15)和6.7%(1/15)。7例EGFR外显子20插入患者的总缓解率(ORR)和疾病控制率(DCR)分别为28.6%(2/7)和100.0%(7/7)。5例奥希替尼治疗后EGFR突变患者的ORR和DCR分别为40.0%(2/5)和100.0%(5/5)。中位随访8.7个月后,中位无进展生存期和总生存期均未达到。最常见的治疗相关不良事件为皮疹(86.7%)、甲沟炎(80.0%)和输液相关反应(60.0%),且大多数为1至2级。3至4级不良事件包括皮疹(33.3%)、谷丙转氨酶升高(13.3%)、γ-谷氨酰转肽酶升高(13.3%)、外周水肿(6.7%)、血栓栓塞(6.7%)、间质性肺病(6.7%)和血小板减少(6.7%)。

结论

阿米万他单抗在伴有EGFR外显子20插入的中国NSCLC患者以及奥希替尼治疗后EGFR突变患者中有效,与西方国家进行的临床试验结果相似。阿米万他单抗耐受性良好,应重点关注皮疹、甲沟炎和输液相关反应等不良事件。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5549/9346162/5dbb5f68e59d/zgfazz-25-7-493-1.jpg

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