Department of Thoracic Oncology, National Hospital Organization Osaka Toneyama Medical Center, Toyonaka, Japan.
Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan.
PLoS One. 2019 Jul 31;14(7):e0220570. doi: 10.1371/journal.pone.0220570. eCollection 2019.
Pembrolizumab is currently approved as a first-line therapy for advanced non-small cell lung cancer (NSCLC) patients with a programed death ligand-1 (PD-L1) expression ≥50%. However, the association between the efficacy of pembrolizumab and PD-L1 expression levels in patients with PD-L1 expression ≥50% has not been fully elucidated.
We retrospectively analyzed patients with advanced NSCLC and a PD-L1 tumor proportion score (TPS) of ≥50% who received pembrolizumab as a first-line therapy at 11 institutions in Japan between February 2017 and January 2018. Patients were divided into TPS 50-89% and TPS 90-100% (ultra-high PD-L1 expression) cohorts.
In total, 149 patients were included: 99 (66.4%) and 50 (33.6%) patients were in the TPS 50-89% and TPS 90-100% cohorts, respectively. Baseline characteristics were similar between the TPS 90-100% and TPS 50-89% cohorts. The objective response rates (ORR) in the TPS 90-100% and TPS 50-89% cohorts were 58.0% and 46.5%, respectively (p = 0.23). Time to treatment failure (TTF) was longer in the TPS 90-100% cohort than in the TPS 50-89% cohort (hazard ratio [HR]: 0.67, 95% confidence interval (CI): 0.42-1.07; p = 0.09). Although TTF within 120 days after the initiation of pembrolizumab therapy was comparable between both cohorts (p = 0.54), TTF after 120 days was significantly longer in the TPS 90-100% cohort than in the TPS 50-89% cohort (HR: 0.22, 95% CI: 0.06-0.87; p = 0.031). Immune related adverse events of grade 3 or more occurred in 16.0% and 19.2% of patients in the TPS 90-100% and TPS 50-89% cohorts, respectively.
The patients with an ultra-high PD-L1 expression continued pembrolizumab therapy longer, driven by a reduced risk of treatment failure in the late phase. PD-L1 expression levels might be a predictive biomarker of a first-line immunotherapy benefit in the late phase among NSCLC patients with TPS ≥50%.
帕博利珠单抗目前被批准用于程序性死亡配体-1（PD-L1）表达≥50%的晚期非小细胞肺癌（NSCLC）患者的一线治疗。然而，PD-L1 表达≥50%的患者中，帕博利珠单抗的疗效与 PD-L1 表达水平之间的关系尚未完全阐明。
我们回顾性分析了 2017 年 2 月至 2018 年 1 月期间，日本 11 家机构接受帕博利珠单抗作为一线治疗的 PD-L1 肿瘤比例评分（TPS）≥50%的晚期 NSCLC 患者。患者被分为 TPS 50-89%和 TPS 90-100%（超高 PD-L1 表达）两组。
共纳入 149 例患者：TPS 50-89%和 TPS 90-100%组分别为 99 例（66.4%）和 50 例（33.6%）。TPS 90-100%和 TPS 50-89%两组患者的基线特征相似。TPS 90-100%组和 TPS 50-89%组的客观缓解率（ORR）分别为 58.0%和 46.5%（p=0.23）。TPS 90-100%组的无进展生存期（PFS）长于 TPS 50-89%组（风险比[HR]：0.67，95%置信区间[CI]：0.42-1.07；p=0.09）。尽管两组患者在帕博利珠单抗治疗开始后 120 天内的无进展生存期无差异（p=0.54），但 TPS 90-100%组在 120 天后的无进展生存期显著长于 TPS 50-89%组（HR：0.22，95%CI：0.06-0.87；p=0.031）。TPS 90-100%组和 TPS 50-89%组患者分别有 16.0%和 19.2%发生 3 级或以上免疫相关不良事件。
超高 PD-L1 表达患者继续接受帕博利珠单抗治疗的时间更长，这是由于晚期治疗失败风险降低所致。PD-L1 表达水平可能是 TPS≥50%的 NSCLC 患者一线免疫治疗晚期获益的预测生物标志物。
