摘要
德曲妥珠单抗(trastuzumab deruxtecan,T-DXd)已在人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)表达乳腺癌、胃癌、肺癌及其他实体瘤等领域的临床试验中证实了显著疗效,其安全性总体可控、可耐受,但其也会导致间质性肺病(interstitial lung disease,ILD).ILD病因多样,不同抗肿瘤药物所致ILD发生率不等,症状表现各异,发病机制尚不明确.T-DXd相关ILD多为1～2级,实施规范化的临床管理措施可降低ILD严重事件的发生率,改善患者预后,有利于实现T-DXd临床获益最大化.本文对ILD的流行病学、病因、高危因素以及药物所致ILD的可能机制进行总结,并重点介绍T-DXd所致ILD的发生率、发生时间以及经规范化临床管理后的ILD发生情况,以帮助读者更好地理解T-DXd治疗前和治疗期间进行规范化临床管理的重要性.在具体的临床管理策略上,本文结合临床研究方案管理标准及国内外真实世界管理经验,从患者筛查、患者教育、ILD监测、诊断和治疗等方面对T-DXd所致ILD全程管理策略进行综述.在接受T-DXd治疗前,患者筛查有助于识别高危ILD风险患者,高危患者应谨慎使用T-DXd.而良好的患者教育可提高患者的主动性,促使其及时报告疑似症状,有助于ILD的早期识别.在T-DXd治疗期间应定期监测ILD患者的相关症状和体征,并通过定期的影像学监测和多学科团队合作尽可能早期诊断ILD,将严重ILD的发生风险降至最低.在出现疑似症状或影像学表现时,必须立即中断T-DXd治疗,在考虑肾上腺皮质激素治疗的同时完善相关检查以排除其他可能病因.确诊ILD后,应根据其严重程度分级决策T-DXd后续剂量调整、肾上腺皮质激素治疗和其他辅助治疗方案.此外,本文结合国内外临床经验针对T-DXd所致ILD患者是否可进行T-DXd再治疗进行了详细讨论,认为1级ILD患者可在特定情况下再次接受T-DXd治疗.综上所述,本文通过梳理T-DXd所致ILD的流行病学、发生及发展特点、临床试验推荐管理策略以及国内外真实世界管理措施,结合临床专家经验对T-DXd所致ILD的全程管理策略进行总结和讨论,以期提高临床医师对T-DXd所致ILD的认知水平,为T-DXd所致ILD的早期识别、及时诊断和妥善管理提供有价值的参考.
Abstract
Trastuzumab deruxtecan(T-DXd)has demonstrated significant efficacy in clinical trials for human epidermal growth factor receptor 2(HER2)-expressing breast cancer,gastric cancer,lung cancer and other solid tumors.Its overall safety profile is manageable and tolerable,including the clinically concerning interstitial lung disease(ILD).The etiology of ILD is varied,among which drug-induced ILD is an exclusionary diagnosis.The incidence of ILD caused by different antitumor drugs varies with different symptoms,and the pathogenesis remains unclear.T-DXd-induced ILD is mostly Grades 1-2,and implementing a standardized clinical management protocol can reduce the incidence of severe ILD events,improve patient prognosis,and help maximize the clinical benefits of T-DXd.This article summarized the epidemiology,etiology,risk factors,and potential mechanisms of drug-induced ILD,with a focus on the incidence,time to onset,and outcomes of T-DXd-induced ILD after standardized clinical management.It aimed to help readers understand the importance of standardized clinical management before and during T-DXd treatment.Regarding specific clinical management strategies,the article reviewed comprehensive management approaches for T-DXd-induced ILD based on clinical trial protocols and real-world experiences from both domestic and international perspectives,covering patient screening,patient education,ILD monitoring,diagnosis,and treatment.Before initiating T-DXd treatment,patient screening helps identify those at high risk for ILD,and T-DXd should be used cautiously in these high-risk patients.Effective patient education can enhance patient initiative,encouraging them to promptly report suspected symptoms,which contributes to early identification of ILD.During T-DXd treatment,it is important to regularly monitor symptoms and signs related to ILD,implement regular imaging monitoring and leverage multidisciplinary team collaboration to diagnose ILD as early as possible,thereby minimizing the risk of severe ILD.If symptoms or imaging suggest ILD,T-DXd treatment must be immediately interrupted,and relevant examinations should be completed to rule out other possible causes while considering corticosteroid treatment.Upon ILD diagnosis,subsequent T-DXd dose adjustments,corticosteroid therapy,and supportive treatments should be guided by severity.The article also explored whether patients with T-DXd-induced ILD can be re-treated,concluding that Grade 1 ILD patients might be eligible for re-treatment under specific conditions.In conclusion,the article reviewed the epidemiology,characteristics,clinical trial-recommended management strategies,and real-world management measures of T-DXd-induced ILD,integrating clinical expert experiences to summarize and discuss comprehensive management strategies for it.This aimed to enhance clinicians'understanding of T-DXd-induced ILD and provide valuable insights for early identification,timely diagnosis,and proper management of it.
国家科技期刊平台
NSTL
维普
万方数据