Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Hebei Clinical Research Center for Radiation Oncology, Shijiazhuang, China.
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Cancer. 2023 Jul 1;129(13):1969-1985. doi: 10.1002/cncr.34755. Epub 2023 Mar 30.
Neoadjuvant immunotherapy (nIT) is a rapidly emerging paradigm for advanced resectable non-small cell lung cancer (NSCLC). The objectives of this PRISMA/MOOSE/PICOD-guided systematic review and meta-analysis were (1) to assess the safety and efficacy of nIT, (2) to compare the safety and efficacy of neoadjuvant chemoimmunotherapy (nCIT) versus chemotherapy alone (nCT), and (3) to explore predictors of pathologic response with nIT and their association with outcomes.
Eligibility was resectable stage I-III NSCLC and the receipt of programmed death-1/programmed cell death ligand-1 (PD-L1)/cytotoxic T-lymphocyte-associated antigen-4 inhibitors before resection; other forms and modalities of neoadjuvant and/or adjuvant therapies were allowed. For statistical analysis, the Mantel-Haenszel fixed-effect or random-effect model was used, depending on the heterogeneity (I ).
Sixty-six articles met the criteria (eight randomized studies, 39 prospective nonrandomized studies, and 19 retrospective studies). The pooled pathologic complete response (pCR) rate was 28.1%. The estimated grade ≥3 toxicity rate was 18.0%. Compared with nCT, nCIT achieved higher rates of pCR (odds ratio [OR], 7.63; 95% confidence interval [CI], 4.49-12.97; p < .001), progression-free survival (PFS) (hazard ratio [HR] 0.51; 95% CI, 0.38-0.67; p < .001), and overall survival (OS) (HR, 0.51; 95% CI, 0.36-0.74; p = .0003) but yielded similar toxicity rates (OR, 1.01; 95% CI, 0.67-1.52; p = .97). The results remained robust on sensitivity analysis when all retrospective publications were removed. pCR was associated with improved PFS (HR, 0.25; 0.15-0.43; p < .001) and OS (HR, 0.26; 95% CI, 0.10-0.67; p = .005). PD-L1 expressors (≥1%) were more likely to achieve a pCR (OR, 2.93; 95% CI, 1.22-7.03; p = .02).
In patients with advanced resectable NSCLC, neoadjuvant immunotherapy was safe and efficacious. nCIT improved pathologic response rates and PFS/OS over nCT, particularly in patients who had tumors that expressed PD-L1, without increasing toxicities.
This meta-analysis of 66 studies showed that neoadjuvant immunotherapy for advanced resectable non-small cell lung cancer is safe and efficacious. Compared with chemotherapy alone, chemoimmunotherapy improved pathologic response rates and survival, particularly for patients who had tumors that expressed programmed cell death ligand-1, without increasing toxicities.
新辅助免疫治疗（nIT）是一种新兴的治疗可切除局部晚期非小细胞肺癌（NSCLC）的方法。本 PRISMA/MOOSE/PICOD 指南指导的系统评价和荟萃分析的目的是：（1）评估 nIT 的安全性和疗效；（2）比较新辅助化疗免疫治疗（nCIT）与单纯化疗（nCT）的安全性和疗效；（3）探索 nIT 预测病理反应的预测因子及其与结果的关系。
纳入标准为可切除的 I-III 期 NSCLC 患者，并在切除前接受程序性死亡受体-1/程序性死亡配体-1（PD-L1）/细胞毒性 T 淋巴细胞相关抗原-4 抑制剂治疗；允许其他形式和方式的新辅助和/或辅助治疗。对于统计分析，取决于异质性（I²），使用 Mantel-Haenszel 固定效应或随机效应模型。
符合条件的 66 篇文章（8 篇随机研究、39 篇前瞻性非随机研究和 19 篇回顾性研究）入选。总的病理完全缓解（pCR）率为 28.1%。估计≥3 级毒性发生率为 18.0%。与 nCT 相比，nCIT 实现了更高的 pCR 率（优势比[OR]，7.63；95%置信区间[CI]，4.49-12.97；p<0.001）、无进展生存期（PFS）（风险比[HR]，0.51；95%CI，0.38-0.67；p<0.001）和总生存期（OS）（HR，0.51；95%CI，0.36-0.74；p=0.0003），但毒性发生率相似（OR，1.01；95%CI，0.67-1.52；p=0.97）。当所有回顾性出版物被删除时，敏感性分析结果仍然稳健。pCR 与改善的 PFS（HR，0.25；0.15-0.43；p<0.001）和 OS（HR，0.26；95%CI，0.10-0.67；p=0.005）相关。PD-L1 表达者（≥1%）更有可能获得 pCR（OR，2.93；95%CI，1.22-7.03；p=0.02）。
在可切除局部晚期 NSCLC 患者中，新辅助免疫治疗是安全有效的。与单纯化疗相比，化疗免疫治疗提高了病理缓解率和 PFS/OS，特别是在 PD-L1 表达的肿瘤患者中，而不增加毒性。
