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新辅助和围手术期免疫疗法在可切除非小细胞肺癌中不断演变作用的证据。

Evidence for the evolving role of neoadjuvant and perioperative immunotherapy in resectable non-small cell lung cancer.

作者信息

Hansen Thomas, Hill Jonathon, Tincknell Gary, Siu Derrick, Brungs Daniel, Clingan Philip, Chantrill Lorraine, Nindra Udit

机构信息

Department of Medical Oncology, St George Hospital, Kogarah, Sydney 2217, NSW, Australia.

Department of Medical Oncology, Wollongong Hospital, Illawarra Shoalhaven Local Health District, Illawarra 2500, NSW, Australia.

出版信息

Explor Target Antitumor Ther. 2024;5(6):1247-1260. doi: 10.37349/etat.2024.00273. Epub 2024 Sep 29.

Abstract

The treatment of early-stage non-small cell lung cancer (NSCLC) is becoming increasingly complex. Standard of care management for the past decade has been adjuvant chemotherapy following curative intent resection regardless of nodal status or tumour profile. With the increased incorporation of immunotherapy in NSCLC, especially in the locally advanced, unresectable, or metastatic settings, multiple studies have sought to assess its utility in early-stage disease. While there are suboptimal responses to neoadjuvant chemotherapy alone, there is a strong rationale for the use of neoadjuvant immunotherapy in tumour downstaging, based upon the concept of enhanced T cell priming at the time of a high tumour antigen burden, and demonstrated clinically in other solid tumours, such as melanoma. In the NSCLC cancer setting, currently over 20 combinations of chemoimmunotherapy in the neoadjuvant and perioperative setting have been studied with results variable. Multiple large phase III studies have demonstrated that neoadjuvant chemoimmunotherapy combinations result in significant advances in pathological response, disease free and overall survival which has led to practice change across the world. Currently, combination immunotherapy regimens with novel agents targeting alternate immunomodulatory pathways are now being investigated. Given this, the landscape of treatment in resectable early-stage NSCLC has become increasingly complex. This review outlines the literature of neoadjuvant and perioperative immunotherapy and discusses its potential benefits and complexities and ongoing considerations into future research.

摘要

早期非小细胞肺癌(NSCLC)的治疗正变得越来越复杂。在过去十年中,无论淋巴结状态或肿瘤特征如何,标准的治疗管理方法都是在根治性切除术后进行辅助化疗。随着免疫疗法在NSCLC治疗中的应用增加,尤其是在局部晚期、不可切除或转移性情况下,多项研究试图评估其在早期疾病中的效用。虽然单独的新辅助化疗反应欠佳,但基于高肿瘤抗原负荷时增强T细胞启动的概念,并在其他实体瘤(如黑色素瘤)中得到临床证实,新辅助免疫疗法在肿瘤降期方面有很强的应用依据。在NSCLC领域,目前已经研究了新辅助和围手术期超过20种化疗免疫疗法组合,结果各不相同。多项大型III期研究表明,新辅助化疗免疫疗法组合在病理反应、无病生存期和总生存期方面取得了显著进展,这导致了全球治疗实践的改变。目前,正在研究针对替代免疫调节途径的新型药物的联合免疫疗法方案。鉴于此,可切除早期NSCLC的治疗格局变得越来越复杂。这篇综述概述了新辅助和围手术期免疫疗法的文献,并讨论了其潜在益处、复杂性以及对未来研究的持续考量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f66/11502072/5d7c3150849b/etat-05-1002273-g001.jpg

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