Amivantamab治疗EGFR/MET基因异常非小细胞肺癌的单中心经验

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

背景与目的表皮生长因子受体(epidermal growth factor receptor,EGFR)和细胞间质上皮转换因子(cellular-mesenchymal to epithelial transition factor,c-Met)是非小细胞肺癌(non-small cell lung cancer,NSCLC)中常见的变异基因,都是受体酪氨酸激酶,在下游信号转导方面具有协同作用。针对EGFR和c-Met通路的靶向药物联合应用后,能够阻断PI3K/AKT/mTOR途径和Ras/Raf/Mek途径,限制补偿通路激活,发挥抗肿瘤作用。以Amivantamab为代表的EGFR和c-Met双特异性抗体新型药物能同时阻断两条信号通路,在肺癌临床研究中展现出良好前景。然而目前国内应用较少,相关经验缺乏。本研究将介绍我中心Amivantamab疗效数据和不良反应处理经验,探讨此类药物对我国EGFR/MET基因异常NSCLC的应用价值。方法收集2020年8月-2021年12月于我院接受Amivantamab治疗的晚期NSCLC病例的临床数据,分析其治疗反应率、生存和不良反应。结果本研究共纳入15例患者,其中Amivantamab单药治疗6例,Amivantamab联合Lazertinib治疗9例。治疗后7例(46.7%)达部分缓解(partial response,PR),7例(46.7%)达疾病稳定(stable disease,SD),1例(6.7%)达疾病进展(progressive disease,PD),总体客观缓解率(objective response rate,ORR)为46.7%,总体疾病控制率(disease control rate,DCR)为93.3%。7例EGFR外显子20插入突变患者中,2例(28.6%)达PR,5例(71.4%)达SD,DCR为100.0%,中位缓解持续时间(duration of response,DOR)未成熟,2例PR者仍持续缓解。5例奥希替尼耐药的患者中,2例(40.0%)达PR,3例(60.0%)达SD,DCR为100.0%,中位DOR未成熟,1例PR者仍持续缓解。中位随访时间为8.7个月(0.9个月-18.6个月),截至最后一次随访,共有6例患者发生疾病进展,3例患者死亡,中位无进展生存期和中位总生存期未成熟。常见的不良事件为皮疹(86.7%),甲沟炎(80.0%)和输液反应(60.0%),多为1级-2级。3级及以上不良反应包括皮疹(33.3%),转氨酶升高(13.3%)、水肿(6.7%)、血栓栓塞(6.7%)、间质性肺炎(6.7%)和血小板减低(6.7%)。结论Amivantamab对EGFR外显子20插入突变和奥希替尼耐药的中国晚期NSCLC治疗有效,与国外疗效数据相仿。整体安全性可耐受,需重点关注皮疹、甲沟炎、输液反应等不良反应。

Background and objective 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%).Conclusion 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.