Jiang Juan, Wang Yuling, Gao Yang, Sugimura Haruhiko, Minervini Fabrizio, Uchino Junji, Halmos Balazs, Yendamuri Sai, Velotta Jeffrey B, Li Min
Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, China.
Xiangya Lung Cancer Center, Xiangya Hospital, Central South University, Changsha, China.
Transl Lung Cancer Res. 2022 Feb;11(2):277-294. doi: 10.21037/tlcr-22-75.
In recent years, a series of clinical trials have explored the application of neoadjuvant immunotherapy or chemoimmunotherapy in non-small cell lung cancer (NSCLC). However, no randomized control trials comparing neoadjuvant immunotherapy with chemoimmunotherapy have yet been reported. This study aimed to summarize and compare the efficacy and safety of neoadjuvant immunotherapy and chemoimmunotherapy in NSCLC.
Literature focusing on the efficacy and safety of neoadjuvant immunotherapy or chemoimmunotherapy in NSCLC published before June 2021 was retrieved from PubMed, Embase, and the Cochrane Library. Study endpoints included major pathological response (MPR), complete pathological response (pCR), treatment-related adverse events (TRAEs), severe adverse events (SAEs), resection rate, surgical delay rate, and conversion to thoracotomy. The risk of bias was assessed using the Cochrane bias risk assessment tool. Subgroup and sensitivity analyses were further performed.
A total of 988 patients from 16 studies were included in this meta-analysis. For patients who received neoadjuvant immunotherapy with single/combined ICIs or chemoimmunotherapy, the pooled MPR rate was 43.5% and the pooled pCR rate was 21.9%. The pooled incidence of TRAEs and SAEs were 54.8% and 15.3%, respectively. The pooled resection rate was 85.8%, the surgical delay rate was 7.4%, and the conversion rate was 17.4%. Patients who received neoadjuvant chemoimmunotherapy had remarkably improved pathological response (MPR rate: 53.3% 28.6%; pCR rate: 28.6% 9.9%) compared with those receiving neoadjuvant single-agent immunotherapy, while the incidence of SAEs (18.0% 12.3%) and surgical delay rate (3.8% 7.4%) did not significantly increase. Neoadjuvant nivolumab combined with ipilimumab also achieved a high pCR rate (28.6%) with tolerable toxicity. Nivolumab- and pembrolizumab-based neoadjuvant therapy showed a higher MPR rate (nivolumab 51.5%, pembrolizumab 46.8%) and pCR rate (nivolumab 29.1%, pembrolizumab 31.5%). Besides, patients with positive programmed death-ligand 1 (PD-L1) expression [tumor proportion score (TPS) ≥1%] exhibited favorable pathological responses than PD-L1 negative patients.
Overall, neoadjuvant immunotherapy or chemoimmunotherapy is effective and safe in NSCLC. Compared with single-agent immunotherapy, neoadjuvant chemoimmunotherapy provides a significant improvement in pathological response without increasing the incidence of SAEs or surgical delay. These results need further confirmation by more large-scale randomized controlled trials.
近年来，一系列临床试验探索了新辅助免疫治疗或化疗免疫治疗在非小细胞肺癌（NSCLC）中的应用。然而，尚无比较新辅助免疫治疗与化疗免疫治疗的随机对照试验报道。本研究旨在总结和比较新辅助免疫治疗与化疗免疫治疗在NSCLC中的疗效和安全性。
从PubMed、Embase和Cochrane图书馆检索2021年6月之前发表的关于新辅助免疫治疗或化疗免疫治疗在NSCLC中的疗效和安全性的文献。研究终点包括主要病理缓解（MPR）、完全病理缓解（pCR）、治疗相关不良事件（TRAEs）、严重不良事件（SAEs）、切除率、手术延迟率和转为开胸手术率。使用Cochrane偏倚风险评估工具评估偏倚风险。进一步进行亚组分析和敏感性分析。
本荟萃分析共纳入了16项研究中的988例患者。对于接受新辅助免疫治疗（单药/联合免疫检查点抑制剂）或化疗免疫治疗的患者，汇总的MPR率为43.5%，汇总的pCR率为21.9%。TRAEs和SAEs的汇总发生率分别为54.8%和15.3%。汇总的切除率为85.8%，手术延迟率为7.4%，转化率为17.4%。与接受新辅助单药免疫治疗的患者相比，接受新辅助化疗免疫治疗的患者病理缓解显著改善（MPR率：53.3%对28.6%；pCR率：28.6%对9.9%），而SAEs发生率（18.0%对12.3%）和手术延迟率（3.8%对7.4%）没有显著增加。新辅助纳武利尤单抗联合伊匹木单抗也实现了较高的pCR率（28.6%）且毒性可耐受。基于纳武利尤单抗和帕博利珠单抗的新辅助治疗显示出较高的MPR率（纳武利尤单抗51.5%，帕博利珠单抗46.8%）和pCR率（纳武利尤单抗29.1%，帕博利珠单抗31.5%）。此外，程序性死亡配体1（PD-L1）表达阳性[肿瘤比例评分（TPS）≥1%]的患者比PD-L1阴性患者表现出更好的病理缓解。
总体而言，新辅助免疫治疗或化疗免疫治疗在NSCLC中是有效且安全的。与单药免疫治疗相比，新辅助化疗免疫治疗在不增加SAEs发生率或手术延迟的情况下，显著改善了病理缓解。这些结果需要更多大规模随机对照试验进一步证实。
