Ohara Akihiro, Mori Taisuke, Itoyama Mai, Yokoyama Kazuki, Yamamoto Shun, Kato Ken, Honma Yoshitaka
Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan.
Cancer Rep (Hoboken). 2025 Jan;8(1):e70125. doi: 10.1002/cnr2.70125.
PD-L1 expression in tumors and immune cells is a biomarker for the efficacy of anti-PD-1 antibody (APA) therapy across diverse cancers. Based on the results from the KEYNOTE-048 trial, pembrolizumab monotherapy is indicated for platinum-sensitive recurrent/metastatic head and neck squamous cell carcinoma (R/M-HNSCC) with a positive combined positive score (CPS). Conversely, nivolumab is utilized for platinum-pretreated R/M-HNSCC regardless of the positive tumor proportion score (TPS) following the results of the CheckMate-141; however, its subgroup analysis indicated that TPS-positive population tended to have a relatively high overall response rate and progression-free survival (PFS). Although, the superior PD-L1 evaluation method for predicting APA therapy efficacy in R/M-HNSCC and the appropriate cut-off value remain undetermined. This study aims to elucidate the relationship between short-term outcomes and PD-L1 expression based on CPS and TPS in R/M-HNSCC patients undergoing APA monotherapy.
R/M-HNSCC patients receiving APA monotherapy from 2018 to 2021 with available samples were enrolled. An experienced pathologist evaluated CPS and TPS utilizing the PD-L1 IHC 22C3 pharmDx assay. Short-term outcomes were assessed by clinical benefit rate (CBR), objective response rate (ORR), and PFS.
Fifty-three R/M-HNSCC patients received APA monotherapy. Forty-seven had CPS ≥ 1, and 44 had TPS ≥ 1%. By receiver-operating characteristic curve analysis, the CPS cut-off value for predicting better CBR was determined to be 50. The ORR/CBR tended to be higher when CPS was positive. Although differences in PFS were not observed for a cut-off value of 1 or 20, they were observed for 50 (3.2 vs. 8.4 months; hazard ratio 0.44, p = 0.02). ORR and CBR were respectively 12.5% and 12.5% in the TPS < 1% group and 33.3% and 48.9% in the ≥ 1% group. The TPS < 1% group showed significantly poorer PFS (1.9 vs. 4.5 months, hazard ratio 0.40, p = 0.01).
The short-term efficacy of APA monotherapy in R/M-HNSCC patients tended to be better when CPS was positive. TPS helps predict the population that does not benefit from APA monotherapy.
肿瘤和免疫细胞中的程序性死亡受体配体1（PD-L1）表达是抗程序性死亡蛋白1抗体（APA）疗法在多种癌症中疗效的生物标志物。基于KEYNOTE-048试验结果，帕博利珠单抗单药疗法适用于联合阳性评分（CPS）为阳性的铂敏感复发/转移性头颈部鳞状细胞癌（R/M-HNSCC）。相反，根据CheckMate-141试验结果，纳武利尤单抗用于铂预处理的R/M-HNSCC，无论肿瘤比例评分（TPS）是否为阳性；然而，其亚组分析表明，TPS阳性人群往往具有相对较高的总缓解率和无进展生存期（PFS）。尽管如此，预测R/M-HNSCC中APA疗法疗效的最佳PD-L1评估方法及合适的临界值仍未确定。本研究旨在阐明接受APA单药治疗的R/M-HNSCC患者短期疗效与基于CPS和TPS的PD-L1表达之间的关系。
纳入2018年至2021年接受APA单药治疗且有可用样本的R/M-HNSCC患者。一名经验丰富的病理学家使用PD-L1免疫组化22C3检测试剂盒评估CPS和TPS。通过临床获益率（CBR）、客观缓解率（ORR）和PFS评估短期疗效。
53例R/M-HNSCC患者接受了APA单药治疗。47例CPS≥1，44例TPS≥1%。通过受试者工作特征曲线分析，预测更好CBR的CPS临界值确定为50。CPS为阳性时，ORR/CBR往往更高。虽然CPS临界值为1或20时未观察到PFS差异，但临界值为50时观察到差异（3.2个月对8.4个月；风险比0.44，p=0.02）。TPS<1%组的ORR和CBR分别为12.5%和12.5%，≥1%组分别为33.3%和48.9%。TPS<1%组的PFS明显更差（1.9个月对4.5个月，风险比0.40，p=0.01）。
CPS为阳性时，APA单药治疗R/M-HNSCC患者的短期疗效往往更好。TPS有助于预测无法从APA单药治疗中获益的人群。
