Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50%
Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50%
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DOI：
10.1007/s00262-020-02613-9
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发表时间：
2020-05-30
影响因子：
5.8
通讯作者：
Porzio, Giampiero
中科院分区：
文献类型：
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作者：
Cortellini, Alessio;Tiseo, Marcello;Porzio, Giampiero
Pembrolizumab单药治疗是PD-L1（程序性死亡配体1）表达>= 50%的转移性非小细胞肺癌（NSCLC）患者的标准一线治疗选择。方法我们进行了一项多中心回顾性研究，旨在评估pembrolizumab在PD-L1表达>= 50%的初治NSCLC患者中的有效性的临床病理相关性。结果1026例患者纳入研究。客观缓解率（ORR）为44.5%（95% CI 40.2-49.1），中位无进展生存期（PFS）和总生存期（OS）分别为7.9个月（95% CI 6.9-9.5; 599起事件）和17.2个月（95% CI 15.3-22.3; 598例删失患者）。经证实，ECOG-PS>= 2（p < 0.0001）和骨转移（p = 0.0003）是ORR恶化的独立预测因素。在多变量分析中，证实既往吸烟者（p = 0.0002），但当前未吸烟者（p = 0.0532）与从不吸烟者相比，PFS显著延长。ECOG-PS（p < 0.0001）、骨转移（p < 0.0001）和肝转移（p < 0.0001）也被证实是PFS恶化的独立预测因素。既往姑息性RT与OS缩短显著相关（p = 0.0104），而既往非姑息性RT与OS延长显著相关（p = 0.0033）。与从不吸烟者相比，证实既往吸烟者（p = 0.0131）但当前未吸烟者（p = 0.3433）的OS显著延长。ECOG-PS（p < 0.0001），骨转移（p < 0.0001）和肝转移（p < 0.0001）也被证实是OS缩短的独立预测因子。通过递归分割评估，PD-L1表达>= 90%与显著较高的ORR相关（p = 0.0204），以及多变量分析时的更长时间和OS（p = 0.0346）。结论Pembrolizumab在临床试验外治疗的大型NSCLC患者队列中有效。关于临床亚组（如PS较差和肝/骨转移患者）的有效性问题仍有待解决。我们证实，没有烟草暴露以及存在骨和肝转移与pembrolizumab的临床结局较差相关。增加PD-L1表达水平可能有助于确定从pembrolizumab单药治疗中获得更大益处的患者子集。
Background Single-agent pembrolizumab represents the standard first-line option for metastatic non-small-cell lung cancer (NSCLC) patients with a PD-L1 (programmed death-ligand 1) expression of >= 50%. Methods We conducted a multicenter retrospective study aimed at evaluating the clinicopathologic correlates of pembrolizumab effectiveness in patients with treatment-naive NSCLC and a PD-L1 expression of >= 50%. Results One thousand and twenty-six consecutive patients were included. The objective response rate (ORR) was 44.5% (95% CI 40.2-49.1), while the median progression free survival (PFS) and overall survival (OS) were 7.9 months (95% CI 6.9-9.5; 599 events) and 17.2 months (95% CI 15.3-22.3; 598 censored patients), respectively. ECOG-PS >= 2 (p < 0.0001) and bone metastases (p = 0.0003) were confirmed to be independent predictors of a worse ORR. Former smokers (p = 0.0002), but not current smokers (p = 0.0532) were confirmed to have a significantly prolonged PFS compared to never smokers at multivariate analysis. ECOG-PS (p < 0.0001), bone metastases (p < 0.0001) and liver metastases (p < 0.0001) were also confirmed to be independent predictors of a worse PFS. Previous palliative RT was significantly related to a shortened OS (p = 0.0104), while previous non-palliative RT was significantly related to a prolonged OS (p = 0.0033). Former smokers (p = 0.0131), but not current smokers (p = 0.3433) were confirmed to have a significantly prolonged OS compared to never smokers. ECOG-PS (p < 0.0001), bone metastases (p < 0.0001) and liver metastases (p < 0.0001) were also confirmed to be independent predictors of a shortened OS. A PD-L1 expression of >= 90%, as assessed by recursive partitioning, was associated with significantly higher ORR (p = 0.0204), and longer and OS (p = 0.0346) at multivariable analysis. Conclusion Pembrolizumab was effective in a large cohort of NSCLC patients treated outside of clinical trials. Questions regarding the effectiveness in clinical subgroups, such as patients with poorer PS and with liver/bone metastases, still remain to be addressed. We confirmed that the absence of tobacco exposure, and the presence of bone and liver metastasis are associated with worse clinical outcomes to pembrolizumab. Increasing levels of PD-L1 expression may help identifying a subset of patients who derive a greater benefit from pembrolizumab monotherapy.