Lu Shuangqing, Wang Chao, Zhai Xiaoyang, Sun Zhuoran, Zhao Ke, Chen Dawei, Zhu Hui
Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.
Ther Adv Med Oncol. 2025 Jul 20;17:17588359251356919. doi: 10.1177/17588359251356919. eCollection 2025.
Immunotherapy combined with chemotherapy is the first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). However, the effect of delayed initiation of immunotherapy on its efficacy remains unclear.
This study aimed to investigate the impact of the delayed addition of programmed death receptor 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors on treatment outcomes in patients with ES-SCLC.
This retrospective cohort study used propensity score matching (PSM) to balance baseline characteristics.
This study included 416 patients with ES-SCLC who received first-line immunotherapy between January 2020 and December 2022. Patients were categorized into two groups: delayed-immunotherapy (IO) (PD-1/PD-L1 inhibitors initiated during the 2nd or 3rd chemotherapy cycle) and early-IO (immunotherapy initiated during the first cycle). A 1:1 PSM was performed to balance baseline characteristics. The primary endpoints were overall survival (OS) and progression-free survival (PFS), which were analyzed using the Kaplan-Meier method and compared using log-rank tests.
Owing to the exclusion of PD-L1/PD-1 inhibitors from medical insurance, financial constraints, and poor physical condition of some patients, 72 patients were included in the delayed-IO group (second cycle: 41; third cycle: 31), while 344 were in the early-IO group. Before PSM, median OS and PFS in the delayed-IO group were 24.00 and 8.75 months, compared to 18.59 and 7.57 months in the early-IO group, with no significant differences (OS: HR 0.72, = 0.054; PFS: HR 0.86, = 0.281). After PSM (72 patients per group), the delayed-IO group showed significantly longer median OS (24.00 vs 18.79 months, HR 0.60, 95% CI 0.38-0.97, = 0.037) and PFS (8.75 vs 6.49 months, HR 0.69, 95% CI 0.48-0.99, = 0.044) compared to the early-IO group. These results suggest that, in specific patient populations, delayed immunotherapy may improve survival outcomes by optimizing patient condition or treatment response.
In patients with ES-SCLC, delayed administration of PD-1/PD-L1 inhibitors during the second to fourth chemotherapy cycles improves survival outcomes compared to concurrent administration during the first cycle, with a similar safety profile. These results suggest that, in specific patient populations, delayed immunotherapy may improve survival outcomes by optimizing patient condition or treatment response.
免疫疗法联合化疗是广泛期小细胞肺癌（ES-SCLC）的一线治疗方案。然而，免疫疗法延迟启动对其疗效的影响尚不清楚。
本研究旨在探讨程序性死亡受体1/程序性死亡配体1（PD-1/PD-L1）抑制剂延迟添加对ES-SCLC患者治疗结局的影响。
本回顾性队列研究采用倾向评分匹配（PSM）来平衡基线特征。
本研究纳入了2020年1月至2022年12月期间接受一线免疫治疗的416例ES-SCLC患者。患者分为两组：延迟免疫治疗（IO）组（在第2或第3化疗周期开始使用PD-1/PD-L1抑制剂）和早期IO组（在第1周期开始免疫治疗）。进行1:1的PSM以平衡基线特征。主要终点为总生存期（OS）和无进展生存期（PFS），采用Kaplan-Meier方法进行分析，并使用对数秩检验进行比较。
由于医疗保险排除了PD-L1/PD-1抑制剂、经济限制以及部分患者身体状况较差，延迟IO组纳入72例患者（第2周期：41例；第3周期：31例），而早期IO组有344例。在PSM之前，延迟IO组的中位OS和PFS分别为24.00个月和8.75个月，早期IO组分别为18.59个月和7.57个月，差异无统计学意义（OS：HR 0.72，P = 0.054；PFS：HR 0.86，P = 0.281）。PSM后（每组72例患者），与早期IO组相比，延迟IO组的中位OS显著更长（24.00个月对18.79个月，HR 0.60，95%CI 0.38 - 0.97，P = 0.037）和PFS显著更长（8.75个月对6.49个月，HR 0.69，95%CI 0.48 - 0.99，P = 0.044）。这些结果表明，在特定患者群体中，延迟免疫治疗可能通过优化患者状况或治疗反应来改善生存结局。
在ES-SCLC患者中，与第1周期同时给药相比，在第2至第4化疗周期延迟给予PD-1/PD-L1抑制剂可改善生存结局，且安全性相似。这些结果表明，在特定患者群体中，延迟免疫治疗可能通过优化患者状况或治疗反应来改善生存结局。
