Fukui Takafumi, Hori Suya, Hatakeyama Yukihisa, Kiriu Tatsunori, Matsumura Kanoko, Miwa Nanako, Katsurada Masahiro, Okuno Keiko, Yoshimura Sho, Tachihara Motoko
Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Division of Respiratory Medicine, Kakogawa Central City Hospital, Kakogawa, Japan.
Anticancer Res. 2025 Sep;45(9):3859-3875. doi: 10.21873/anticanres.17745.
The optimal treatment for advanced non-small-cell lung cancer (NSCLC) with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 1-49% remains unknown. Further stratification by PD-L1 TPS may lead to optimization of treatment.
We conducted a multicenter, retrospective, observational study to compare nivolumab and ipilimumab with/without chemotherapy (dual-therapy group) and chemotherapy with a single-agent immune checkpoint inhibitor (ICI) (single-therapy group) as the first-line therapy for advanced NSCLC with a PD-L1 TPS of 1-49%. The primary endpoint was overall survival in the propensity score-matched population.
A total of 139 patients were enrolled; 113 in the single- (81.3%) and 26 in the dual- (18.7%) therapy groups. In the population with PD-L1 TPS of 1-20%, after propensity score-matching was performed, the median overall survival was 12.0 months for the single-therapy group, but was not reached for the dual-therapy group (=0.022). The median progression-free survival was 6.9 and 11.5 months, respectively (=0.02). In the population with PD-L1 TPS of 21-49%, after propensity score-matching, the median overall survival was not reached for the single-therapy group, but was 9.0 months for the dual-therapy group (=0.04), whilst corresponding median progression-free survival was 8.3 and 4.1 months (=0.087).
The results of this study suggest that in patients with NSCLC, the optimal treatment regimen may differ between those with PD-L1 TPS of 1-20% and 21-49%; moreover, nivolumab and ipilimumab-based therapy may be more effective than chemotherapy with a single-agent ICI for treating advanced NSCLC with ultra-low PD-L1 expression, particularly in those with a PD-L1 TPS of 1-20%.
程序性死亡配体1（PD-L1）肿瘤比例评分（TPS）为1%-49%的晚期非小细胞肺癌（NSCLC）的最佳治疗方案尚不清楚。根据PD-L1 TPS进一步分层可能会优化治疗。
我们进行了一项多中心、回顾性、观察性研究，比较纳武利尤单抗和伊匹木单抗联合或不联合化疗（双药治疗组）以及化疗联合单药免疫检查点抑制剂（ICI）（单药治疗组）作为PD-L1 TPS为1%-49%的晚期NSCLC的一线治疗方案。主要终点是倾向评分匹配人群的总生存期。
共纳入139例患者；单药治疗组113例（81.3%），双药治疗组26例（18.7%）。在PD-L1 TPS为1%-20%的人群中，进行倾向评分匹配后，单药治疗组的中位总生存期为12.0个月，而双药治疗组未达到（P=0.022）。中位无进展生存期分别为6.9个月和11.5个月（P=0.02）。在PD-L1 TPS为21%-49%的人群中，倾向评分匹配后，单药治疗组的中位总生存期未达到，而双药治疗组为9.0个月（P=0.04），相应的中位无进展生存期分别为8.3个月和4.1个月（P=0.087）。
本研究结果表明，在NSCLC患者中，PD-L1 TPS为1%-20%和21%-49%的患者的最佳治疗方案可能不同；此外，对于治疗PD-L1表达极低的晚期NSCLC，基于纳武利尤单抗和伊匹木单抗的治疗可能比化疗联合单药ICI更有效，尤其是在PD-L1 TPS为1%-20%的患者中。
