背景:新辅助免疫疗法(nIT)是治疗晚期可切除非小细胞肺癌(NSCLC)的迅速发展的范例。本PRISMA/MOOSE/PICOD指导的系统评价和荟萃分析的目的是(1)评估nIT的安全性和有效性,(2)比较新辅助化疗(nCIT)与单纯化疗(nCT)的安全性和有效性,(3)探讨nIT病理反应的预测因素及其与结局的关系。
方法:合格为可切除的I-III期NSCLC,并在切除前接受程序性死亡-1/程序性细胞死亡配体-1(PD-L1)/细胞毒性T淋巴细胞相关抗原-4抑制剂;允许其他形式和方式的新辅助和/或辅助治疗。为了进行统计分析,使用了Mantel-Haenszel固定效应或随机效应模型,取决于异质性(I2)。
结果:66篇文章符合标准(8项随机研究,39项前瞻性非随机研究,和19项回顾性研究)。合并病理完全缓解(pCR)率为28.1%。估计≥3级毒性率为18.0%。与nCT相比,nCIT实现了更高的pCR率(比值比[OR],7.63;95%置信区间[CI],4.49-12.97;p<.001),无进展生存期(PFS)(风险比[HR]0.51;95%CI,0.38-0.67;p<.001),和总生存率(OS)(HR,0.51;95%CI,0.36-0.74;p=.0003),但产生相似的毒性率(OR,1.01;95%CI,0.67-1.52;p=0.97)。删除所有回顾性出版物后,敏感性分析的结果仍然可靠。pCR与改善的PFS(HR,0.25;0.15-0.43;p<.001)和OS(HR,0.26;95%CI,0.10-0.67;p=.005)。PD-L1表达因子(≥1%)更有可能达到pCR(OR,2.93;95%CI,1.22-7.03;p=.02)。
结论:在晚期可切除的非小细胞肺癌患者中,新辅助免疫治疗是安全有效的.与nCT相比,nCIT改善了病理反应率和PFS/OS,特别是在肿瘤表达PD-L1的患者中,毒性没有增加。
结论:这项对66项研究的荟萃分析显示,新辅助免疫治疗治疗晚期可切除非小细胞肺癌是安全有效的。与单纯化疗相比,化学免疫疗法提高了病理反应率和生存率,特别是对于那些表达程序性细胞死亡配体-1的肿瘤患者,而没有增加毒性。
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 (I2 ).
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.