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新辅助免疫检查点抑制剂治疗可切除非小细胞肺癌患者的安全性和有效性:系统评价。

Safety and Efficacy of Neoadjuvant Immune Checkpoint Inhibitor Therapy in Patients with Resectable Non-small-Cell Lung Cancer: A Systematic Review.

机构信息

Thoracic Surgery Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli No 17, Beijing, 100021, People's Republic of China.

出版信息

Target Oncol. 2021 Jul;16(4):425-434. doi: 10.1007/s11523-021-00818-1. Epub 2021 May 13.

Abstract

BACKGROUND

Non-small-cell lung cancer (NSCLC) accounts for most new diagnoses of lung cancer, with high morbidity and mortality worldwide. Immune checkpoint inhibitor (ICI) therapy has transformed the treatment of metastatic and advanced NSCLC. For resectable NSCLC, while surgery is the cornerstone of standard treatment, a number of clinical trials of neoadjuvant immunotherapy have been conducted.

OBJECTIVE

To perform a systematic review on the safety and efficacy of neoadjuvant ICI therapy in patients with resectable NSCLC.

METHODS

This systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We undertook a comprehensive literature search of PubMed, Embase, Cochrane Library, and abstracts and posters from annual meetings of the major oncology societies, American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), American Association for Cancer Research (AACR) up until 29 April 2021.

RESULTS

A total of 399 patients were identified from six articles and four meeting abstracts. 229, 140, and 30 patients received anti-programmed cell death ligand 1 therapy (anti-PD-L1, atezolizumab and durvalumab), anti-programmed cell death 1 therapy (anti-PD-1, nivolumab, pembrolizumab, sintilimab), and anti-PD-1/anti-CTLA-4 combination therapy (nivolumab and ipilimumab), respectively. 255 patients received only ICI therapy before surgery, and 144 patients received ICI and chemotherapy. While ICI therapy was generally well tolerated, grade 3 or higher immune-related adverse events were observed in 13 of 144 patients (9.0%) in the five studies that reported such adverse events data. Patients displayed an overall mean surgical resection rate of 87.5% (349/399, range, 66.7-100%), a surgical delay rate of 1.4%, and an incidence of surgical complications of 21%. On average, 45.6% (159/349), (range 17-83%) of patients exhibited major pathological response (MPR), while 76/349 (21.8%) patients achieved pathological complete response (pCR). In the studies with patients undergoing ICI and chemotherapy, the MPR rate was 66.7% and pCR rate was 35.4%.

CONCLUSIONS

ICI neoadjuvant therapy may be a safe and efficacious treatment option in patients with resectable NSCLC. Combined with chemotherapy, ICI appears to be more efficacious, but displays more adverse events. More ongoing clinical trials will shed further light on the safety and efficacy of ICI neoadjuvant therapy in patients with resectable NSCLC.

摘要

背景

非小细胞肺癌(NSCLC)占肺癌新诊断病例的大多数,在全球范围内发病率和死亡率都很高。免疫检查点抑制剂(ICI)治疗改变了转移性和晚期 NSCLC 的治疗方法。对于可切除的 NSCLC,虽然手术是标准治疗的基石,但已经进行了许多新辅助免疫治疗的临床试验。

目的

对可切除 NSCLC 患者新辅助 ICI 治疗的安全性和疗效进行系统评价。

方法

本系统评价按照 PRISMA(系统评价和荟萃分析的首选报告项目)指南进行。我们对 PubMed、Embase、Cochrane 图书馆以及主要肿瘤学会年会的摘要和海报进行了全面的文献检索,包括美国临床肿瘤学会(ASCO)、欧洲肿瘤内科学会(ESMO)、美国癌症研究协会(AACR)年会,检索时间截至 2021 年 4 月 29 日。

结果

从 6 篇文章和 4 篇会议摘要中总共确定了 399 名患者。229 名、140 名和 30 名患者分别接受了抗程序性死亡配体 1 治疗(抗 PD-L1,阿替利珠单抗和度伐鲁单抗)、抗程序性死亡 1 治疗(抗 PD-1,纳武利尤单抗、帕博利珠单抗、替雷利珠单抗)和抗 PD-1/抗细胞毒性 T 淋巴细胞相关抗原 4 联合治疗(纳武利尤单抗和伊匹单抗)。255 名患者仅在手术前接受 ICI 治疗,144 名患者接受 ICI 和化疗。虽然 ICI 治疗总体上耐受性良好,但在报告此类不良事件数据的五项研究中,有 13 名(9.0%)患者出现了 3 级或更高的免疫相关不良事件。患者的总体平均手术切除率为 87.5%(349/399,范围 66.7-100%),手术延迟率为 1.4%,手术并发症发生率为 21%。平均而言,45.6%(159/349)(范围 17-83%)的患者表现出主要病理缓解(MPR),而 76/349(21.8%)的患者达到病理完全缓解(pCR)。在接受 ICI 和化疗的患者中,MPR 率为 66.7%,pCR 率为 35.4%。

结论

ICI 新辅助治疗可能是可切除 NSCLC 患者的一种安全有效的治疗选择。与化疗联合使用时,ICI 似乎更有效,但显示出更多的不良反应。更多正在进行的临床试验将进一步阐明 ICI 新辅助治疗在可切除 NSCLC 患者中的安全性和疗效。

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