Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
Department of Biotechnology and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Thorac Cancer. 2021 Mar;12(6):880-889. doi: 10.1111/1759-7714.13852. Epub 2021 Feb 1.
Improved outcome in tobacco smoking patients with non-small cell lung cancer (NSCLC) following immunotherapy has previously been reported. However, little is known regarding this association during first-line immunotherapy in patients with high PD-L1 expression. In this study we compared clinical outcomes according to the smoking status of two large multicenter cohorts.
We compared clinical outcomes according to the smoking status (never smokers vs. current/former smokers) of two retrospective multicenter cohorts of metastatic NSCLC patients, treated with first-line pembrolizumab and platinum-based chemotherapy.
A total of 962 NSCLC patients with PD-L1 expression ≥50% who received first-line pembrolizumab and 462 NSCLC patients who received first-line platinum-based chemotherapy were included in the study. Never smokers were confirmed to have a significantly higher risk of disease progression (hazard ratio [HR] = 1.49 [95% CI: 1.15-1.92], p = 0.0022) and death (HR = 1.38 [95% CI: 1.02-1.87], p = 0.0348) within the pembrolizumab cohort. On the contrary, a nonsignificant trend towards a reduced risk of disease progression (HR = 0.74 [95% CI: 0.52-1.05], p = 0.1003) and death (HR = 0.67 [95% CI: 0.45-1.01], p = 0.0593) were reported for never smokers within the chemotherapy cohort. After a random case-control matching, 424 patients from both cohorts were paired. Within the matched pembrolizumab cohort, never smokers had a significantly shorter progression-free survival (PFS) (HR = 1.68 [95% CI: 1.17-2.40], p = 0.0045) and a nonsignificant trend towards a shortened overall survival (OS) (HR = 1.32 [95% CI: 0.84-2.07], p = 0.2205). On the contrary, never smokers had a significantly longer PFS (HR = 0.68 [95% CI: 0.49-0.95], p = 0.0255) and OS (HR = 0.66 [95% CI: 0.45-0.97], p = 0,0356) compared to current/former smoker patients within the matched chemotherapy cohort. On pooled multivariable analysis, the interaction term between smoking status and treatment modality was concordantly statistically significant with respect to ORR (p = 0.0074), PFS (p = 0.0001) and OS (p = 0.0020), confirming the significantly different impact of smoking status across the two cohorts.
Among metastatic NSCLC patients with PD-L1 expression ≥50% receiving first-line pembrolizumab, current/former smokers experienced improved PFS and OS. On the contrary, worse outcomes were reported among current/former smokers receiving first-line chemotherapy.
先前已有报道称，免疫疗法可改善非小细胞肺癌（NSCLC）患者的吸烟状况。然而，对于 PD-L1 高表达患者的一线免疫治疗中这种关联，我们知之甚少。在本研究中，我们比较了两个大型多中心队列中患者的吸烟状况。
我们比较了两个转移性 NSCLC 患者的多中心回顾性队列的吸烟状况（从不吸烟者与当前/前吸烟者），这些患者接受了一线 pembrolizumab 和铂类化疗治疗。
共有 962 名 PD-L1 表达≥50%的 NSCLC 患者接受了一线 pembrolizumab 治疗，462 名 NSCLC 患者接受了一线铂类化疗。从不吸烟者被证实疾病进展的风险显著增加（危险比 [HR] = 1.49 [95%CI：1.15-1.92]，p = 0.0022），死亡风险也显著增加（HR = 1.38 [95%CI：1.02-1.87]，p = 0.0348）。相反，在化疗组中，从不吸烟者疾病进展的风险（HR = 0.74 [95%CI：0.52-1.05]，p = 0.1003）和死亡风险（HR = 0.67 [95%CI：0.45-1.01]，p = 0.0593）呈降低趋势，但无统计学意义。经随机病例对照匹配后，两个队列各有 424 例患者配对。在匹配的 pembrolizumab 队列中，从不吸烟者的无进展生存期（PFS）明显缩短（HR = 1.68 [95%CI：1.17-2.40]，p = 0.0045），总生存期（OS）也呈缩短趋势（HR = 1.32 [95%CI：0.84-2.07]，p = 0.2205）。相反，从不吸烟者的 PFS（HR = 0.68 [95%CI：0.49-0.95]，p = 0.0255）和 OS（HR = 0.66 [95%CI：0.45-0.97]，p = 0.0356）明显长于当前/前吸烟者。在多变量分析中，吸烟状况和治疗方式之间的交互项在 ORR（p = 0.0074）、PFS（p = 0.0001）和 OS（p = 0.0020）方面均具有统计学意义，证实了两组之间吸烟状况的显著不同影响。
在 PD-L1 表达≥50%的接受一线 pembrolizumab 治疗的转移性 NSCLC 患者中，当前/前吸烟者的 PFS 和 OS 得到改善。相反，当前/前吸烟者接受一线化疗的预后较差。
