Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
Auris Nasus Larynx. 2020 Aug;47(4):676-686. doi: 10.1016/j.anl.2020.04.001. Epub 2020 May 19.
Our facility measures programmed cell death ligand 1 (PD-L1) expression in all patients before administering nivolumab. The aim of the present study is to clarify the association between overall survival (OS) and PD-L1 expression.
Subjects in this study were 52 patients with R/M-HNC cancer (45 men, 7 women) administered nivolumab in our facility between June 1, 2017 and January 31, 2019. Mean age was 62.2 years (median, 65 years; range, 28-81 years). Histopathological type was squamous cell carcinoma (SCC) in 48 cases, and non-SCC in 4 cases. We set OS as the primary endpoint and progression-free survival (PFS), overall response rate (ORR), association of OS and PD-L1 expression and association of PFS and PD-L1 expression as secondary endpoints. The cut-off for PD-L1 expression was set using the receiver operating characteristic (ROC) curve. We compared OS, PES and ORR using this PD-L1 cut-off for all patients and for the SCC group. OS and PFS were calculated using Kaplan-Meier methods. The log-rank test was used for statistical analysis, with values of p < 0.05 taken as significant. For PD-L1 immunohistochemistry assays, Dako 28-8 antibody was used.
In the all-patients group, median OS was 9.6 months and 1-year OS rate was 40.4%. Median PFS was 4.0 months and 1-year PFS rate was 37.8%. The cut-off value of PD-L1 expression for OS was 40% for all patients and the SCC group. When PD-L1 expression was ≥40%, OS was significantly better in both all patients and the SCC group (p = 0.004, 0.007). The cut-off value of PD-L1 expression for PFS was also 40%. When PD-L1 expression was ≥40%, PFS was better in all patients and the SCC group (P = 0.003, 0.009). In the all-patients group, ORR was 19.2% and disease control rate (DCR) was 44.2%. When PD-L1 expression was ≥40%, ORR was 44.4% and DCR 83.3%.
In the present study, when PD-L1 expression was high (≥40%), OS was significantly better (p = 0.004). This finding has not been reported in other research on R/M-HNC. PFS and ORR were also better with high PD-L1 expression. Regarding patterns of progression with a PD-L1 expression cut-off of 40%, hyperprogression was significantly more frequent for PD-L1 expression <40% (p = 0.039). Therefore, high PD-L1 expression could offer a predictor of prognosis and efficacy for nivolumab. The present findings may prove useful in considering treatment strategies.
本机构在为患者施予纳武利尤单抗前，会对所有患者的程序性细胞死亡配体 1（PD-L1）表达进行测定。本研究旨在明确总生存期（OS）与 PD-L1 表达之间的关联。
本研究对象为在本机构于 2017 年 6 月 1 日至 2019 年 1 月 31 日期间接受纳武利尤单抗治疗的 52 例转移性或复发性头颈部癌症（R/M-HNC）患者（男 45 例，女 7 例）。患者平均年龄为 62.2 岁（中位数，65 岁；范围，28-81 岁）。组织病理学类型为鳞状细胞癌（SCC）48 例，非 SCC 4 例。我们将 OS 作为主要终点，无进展生存期（PFS）、总缓解率（ORR）、OS 与 PD-L1 表达的相关性以及 PFS 与 PD-L1 表达的相关性作为次要终点。使用受试者工作特征（ROC）曲线设定 PD-L1 表达的截断值。我们使用该 PD-L1 截断值比较了所有患者和 SCC 组的 OS、PES 和 ORR。使用 Kaplan-Meier 方法计算 OS 和 PFS。使用对数秩检验进行统计学分析，p 值<0.05 被认为具有统计学意义。对于 PD-L1 免疫组化检测，使用 Dako 28-8 抗体。
在所有患者组中，中位 OS 为 9.6 个月，1 年 OS 率为 40.4%。中位 PFS 为 4.0 个月，1 年 PFS 率为 37.8%。对于所有患者和 SCC 组，PD-L1 表达的 OS 截断值为 40%。当 PD-L1 表达≥40%时，两组患者的 OS 均显著改善（p=0.004，0.007）。PD-L1 表达的 PFS 截断值也为 40%。当 PD-L1 表达≥40%时，两组患者的 PFS 均有所改善（P=0.003，0.009）。在所有患者组中，ORR 为 19.2%，疾病控制率（DCR）为 44.2%。当 PD-L1 表达≥40%时，ORR 为 44.4%，DCR 为 83.3%。
本研究中，当 PD-L1 表达较高（≥40%）时，OS 显著改善（p=0.004）。这一发现与其他 R/M-HNC 研究不同。高 PD-L1 表达还可改善 PFS 和 ORR。关于 PD-L1 表达截断值为 40%时的进展模式，PD-L1 表达<40%的患者中，超进展的发生率显著更高（p=0.039）。因此，高 PD-L1 表达可能是预测纳武利尤单抗预后和疗效的生物标志物。本研究结果可能有助于制定治疗策略。
