一线帕博利珠单抗治疗 PD-L1 表达水平≥50%的晚期 NSCLC 患者的疗效与临床病理相关性分析。
Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50.
机构信息
Medical Oncology, St. Salvatore Hospital, L'Aquila, Italy.
Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy.
出版信息
Cancer Immunol Immunother. 2020 Nov;69(11):2209-2221. doi: 10.1007/s00262-020-02613-9. Epub 2020 May 30.
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-naïve 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.
背景
对于 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，单药派姆单抗代表了标准的一线治疗选择。
方法
我们进行了一项多中心回顾性研究，旨在评估派姆单抗在 PD-L1 表达≥50%的初治 NSCLC 患者中的疗效的临床病理相关性。
结果
共纳入 1026 例连续患者。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 例事件）和 17.2 个月（95%CI 15.3-22.3；598 例删失患者）。ECOG-PS≥2（p<0.0001）和骨转移（p=0.0003）被确认为 ORR 更差的独立预测因素。多变量分析证实，与从不吸烟者相比，既往吸烟者（p=0.0002）而非当前吸烟者（p=0.0532）的 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 更差的独立预测因素。既往姑息性放疗与 OS 缩短显著相关（p=0.0104），而既往非姑息性放疗与 OS 延长显著相关（p=0.0033）。与从不吸烟者相比，既往吸烟者（p=0.0131）而非当前吸烟者（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 缩短的独立预测因素。通过递归分区评估，PD-L1 表达≥90%与显著更高的 ORR（p=0.0204）和更长的 OS（p=0.0346）相关，在多变量分析中。
结论
派姆单抗在临床试验之外的大量 NSCLC 患者中是有效的。关于临床亚组（如 PS 较差的患者和有肝/骨转移的患者）有效性的问题仍有待解决。我们证实，无烟草暴露，以及存在骨和肝转移与派姆单抗治疗的临床结局较差相关。PD-L1 表达水平的升高可能有助于确定从派姆单抗单药治疗中获益更大的患者亚群。
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