Shao Lan, Lou Guangyuan
Department of Medical Oncology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.
J Thorac Dis. 2022 Sep;14(9):3565-3574. doi: 10.21037/jtd-22-1192.
Immune checkpoint inhibitors and immunotherapy have been shown to improve survival rates, especially in non-small cell lung cancer (NSCLC) patients. More recently, several trials have evaluated the clinical roles of immunotherapy as neoadjuvant settings for NSCLC. There trials suggested that neoadjuvant immunotherapy may effectively reduce the risk of the local recurrence and metastasis of cancer, and significantly improved overall survival and cure rates. Here we conducted a review to summarize the possible mechanism, clinical development, and research progress of neoadjuvant immunotherapy in NSCLC.
Relevant articles for this review were retrieved from Google Scholar, Clinicaltrials.gov., and PubMed using the terms "non-small-cell lung cancer", "NSCLC", "neoadjuvant", "immunotherapy", "immune checkpoint inhibitors", "mechanisms", and "toxicity". The primary focus was placed on clinical studies and conference abstracts measuring the safety and efficacy of neoadjuvant immunotherapy in NSCLC until May 2022.
After reviewing the preclinical and clinical trial, the preclinical study showed that neoadjuvant immune checkpoint inhibitor promotes antitumor immunity through the enhancement of T cell effector function and the induction of long-term memory. The initial results of preliminary early-phase trials suggested that neoadjuvant immunotherapy is a promising therapeutic strategy for resectable NSCLC patients, with long-term response and modest toxicity, many of these regimens are currently being evaluated by randomized phase III trials. In addition, the major pathologic response of neoadjuvant immunotherapy ranged up to 45% in these studies when used alone, and up to around 83-86% when used in combination with chemotherapy, therefore it has been seen as a rather potent tumor debulking agent.
Neoadjuvant immunotherapy has been shown to be a novel integral component of NSCLC care. However, there are also several research questions that requires further investigation, such as the side effects, the optimally treated patients, and the time of preoperative immunotherapy.
免疫检查点抑制剂和免疫疗法已被证明可提高生存率,尤其是在非小细胞肺癌(NSCLC)患者中。最近,多项试验评估了免疫疗法作为NSCLC新辅助治疗方案的临床作用。这些试验表明,新辅助免疫疗法可有效降低癌症局部复发和转移的风险,并显著提高总生存率和治愈率。在此,我们进行了一项综述,以总结NSCLC新辅助免疫疗法的可能机制、临床进展和研究成果。
本综述的相关文章通过使用“非小细胞肺癌”“NSCLC”“新辅助”“免疫疗法”“免疫检查点抑制剂”“机制”和“毒性”等关键词,从谷歌学术、Clinicaltrials.gov和PubMed中检索。主要关注截至2022年5月测量NSCLC新辅助免疫疗法安全性和有效性的临床研究和会议摘要。
在回顾临床前和临床试验后,临床前研究表明,新辅助免疫检查点抑制剂通过增强T细胞效应功能和诱导长期记忆来促进抗肿瘤免疫。初步早期试验的初步结果表明,新辅助免疫疗法对于可切除的NSCLC患者是一种有前景的治疗策略,具有长期疗效和适度的毒性,目前许多此类方案正在通过随机III期试验进行评估。此外,在这些研究中,新辅助免疫疗法单独使用时主要病理缓解率高达45%,与化疗联合使用时高达约83-86%,因此它被视为一种相当有效的肿瘤减积剂。
新辅助免疫疗法已被证明是NSCLC治疗的一个新的重要组成部分。然而,仍有几个研究问题需要进一步研究,如副作用、最适合治疗的患者以及术前免疫治疗的时间。