Wankhede Durgesh, Hofman Paul, Grover Sandeep
Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India.
Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, University Côte d'Azur, 30 avenue de la voie romaine, 06002, Nice, France.
J Cancer Res Clin Oncol. 2023 May;149(5):2179-2189. doi: 10.1007/s00432-022-04286-6. Epub 2022 Aug 19.
PD-1/PD-L1 inhibitors prolong survival in treatment-naïve, locally advanced, and metastatic non-small cell lung cancer (NSCLC) with positive PD-L1 expression (> 1%/ > 50%). Recent evidence has suggested that tumors with < 1% PD-L1 expression may also be predictive of PD-1/PD-L1 inhibiting agents.
Systematic review and meta-analysis were conducted of randomized controlled trials (RCTs) evaluating PD-1/PD-L1 inhibitors that have assessed tumors with < 1% PD-L1 expression (negative PD-L1 expression). PD-1/PD-L1 inhibitors-chemotherapy combinations (PC) were compared with histology-selected chemotherapy with respect to overall survival (OS) and progression-free survival (PFS).
Twelve RCTs comprising 5410 participants (PD-1/PD-L1 inhibitors-chemotherapy: 3051; chemotherapy: 2359) met the inclusion criteria. Tumors with PD-L1 expression < 1% were evident in 38.9% of the pooled study population. A significant OS [hazard ratio (HR) 0.71 95% confidence interval (CI) 0.63-0.80, p < 0.00001] and PFS [HR 0.65 95% CI 0.58-0.72, p < 0.00001] benefit of PC was evident in tumors with negative PD-L1 expression. PD-1/PD-L1 inhibitors-chemotherapy combinations were more likely to achieve an objective response than chemotherapy [odds ratio, 1.86; 95% CI, 1.46-2.38, p < 0.00001]. Histologic subtypes and diagnostic assays did not modify the OS and PFS treatment effects for PC compared to chemotherapy.
Tumors harboring < 1% PD-L1 expression are likely to benefit from PD-1/PD-L1 inhibitor-chemotherapy regimens in advanced NSCLC.
PD-1/PD-L1抑制剂可延长初治、局部晚期和转移性非小细胞肺癌（NSCLC）患者的生存期，这些患者的PD-L1表达呈阳性（>1%/>50%）。最近有证据表明，PD-L1表达<1%的肿瘤也可能对PD-1/PD-L1抑制剂有反应。
对评估PD-1/PD-L1抑制剂的随机对照试验（RCT）进行系统评价和荟萃分析，这些试验评估了PD-L1表达<1%（PD-L1表达阴性）的肿瘤。将PD-1/PD-L1抑制剂-化疗联合方案（PC）与根据组织学选择的化疗方案在总生存期（OS）和无进展生存期（PFS）方面进行比较。
12项RCT（共5410名参与者，PD-1/PD-L1抑制剂-化疗组：3051名；化疗组：2359名）符合纳入标准。在汇总研究人群中，38.9%的患者肿瘤PD-L1表达<1%。在PD-L1表达阴性的肿瘤中，PC方案在OS[风险比（HR）0.71，95%置信区间（CI）0.63-0.80，p < 0.00001]和PFS[HR 0.65，95%CI 0.58-0.72，p < 0.00001]方面有显著获益。与化疗相比，PD-1/PD-L1抑制剂-化疗联合方案更有可能实现客观缓解[优势比，1.86；95%CI，1.46-2.38，p < 0.00001]。与化疗相比，组织学亚型和诊断检测并未改变PC方案对OS和PFS的治疗效果。
在晚期NSCLC中，PD-L1表达<1%的肿瘤可能从PD-1/PD-L1抑制剂-化疗方案中获益。
