He Xinyi, Shi Mengting, Zhang Lin, Zhan Jianhua, Liu Jiaqing, Sun Dongchen, Chen Zihong, Hong Shaodong, Zhang Yaxiong, Chen Gang, Zhao Shen, Zhou Ting, Fang Wenfeng, Zhao Yuanyuan, Huang Yan, Zhou Caicun, Yang Yunpeng, Zhang Li, Zhou Huaqiang
Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou University Medical College, Shantou, China.
BMC Cancer. 2025 Aug 27;25(1):1380. doi: 10.1186/s12885-025-14755-z.
Baseline tumor burden (TB), measured radiographically, has emerged as a potential biomarker for stratifying survival outcomes with immune checkpoint inhibitors (ICI) across solid tumors. However, the predictive value for ICI plus chemotherapy (chemoimmunotherapy) in NSCLC has not been confirmed with large cohorts that include a chemotherapy-only control group.
This post hoc analysis utilized data from ORIENT-11 trial, a phase III, randomized clinical trial of advanced NSCLC patients who were administered with either chemoimmunotherapy or chemotherapy alone. TB was measured as the sum of the diameters of target lesions at baseline following RECIST 1.1 criteria. The relationships between baseline TB and outcomes were assessed using the Cox proportional hazards model. Validation was conducted using data from ORIENT-12 trial.
In chemoimmunotherapy arm, patients with low TB demonstrated longer progression-free survival (PFS: 11.60 vs. 7.20 months, hazard ratio [HR] = 0.625, = 0.004) and overall survival (OS: 28.77 vs. 20.10 months, HR = 0.683, = 0.020) compared to those with high TB. In the chemotherapy-only arm, no significant survival differences were observed based on TB levels. Multivariate analyses confirmed that regardless of tumoral PD-L1 expression, low TB as an independent marker of improved survival with chemoimmunotherapy. Patients with high TB and low PD-L1 expression had the shortest survival, deriving minimal benefit from chemoimmunotherapy over chemotherapy alone (PFS: 5.53 vs. 5.07 months; OS: 10.52 vs. 13.80 months). These findings were validated in ORIENT-12 cohort.
Baseline TB is a predictive, rather than prognostic, clinical biomarker for survival outcomes in advanced NSCLC patients treated with chemoimmunotherapy. TB assessment, integrated with PD-L1 status evaluation, may improve patient stratification for first-line chemoimmunotherapy in clinical practice and provide valuable insight for the clinical trials designs.
The online version contains supplementary material available at 10.1186/s12885-025-14755-z.
通过影像学测量的基线肿瘤负荷（TB）已成为一种潜在的生物标志物，可用于对实体瘤患者使用免疫检查点抑制剂（ICI）后的生存结果进行分层。然而，在非小细胞肺癌（NSCLC）中，ICI联合化疗（化疗免疫疗法）的预测价值尚未在包括单纯化疗对照组的大型队列研究中得到证实。
本事后分析利用了ORIENT-11试验的数据，这是一项III期随机临床试验，受试对象为接受化疗免疫疗法或单纯化疗的晚期NSCLC患者。TB按照RECIST 1.1标准测量为基线时靶病灶直径之和。使用Cox比例风险模型评估基线TB与预后之间的关系。并利用ORIENT-12试验的数据进行验证。
在化疗免疫疗法组中，与高TB患者相比，低TB患者的无进展生存期更长（PFS：11.60个月对7.20个月，风险比[HR]=0.625，P=0.004），总生存期也更长（OS：28.77个月对20.10个月，HR=0.683，P=0.020）。在单纯化疗组中，未观察到基于TB水平的显著生存差异。多变量分析证实，无论肿瘤程序性死亡受体配体1（PD-L1）表达如何，低TB都是化疗免疫疗法改善生存的独立标志物。高TB且低PD-L1表达的患者生存期最短，与单纯化疗相比，从化疗免疫疗法中获益最小（PFS：5.53个月对5.07个月；OS：10.52个月对13.80个月）。这些发现已在ORIENT-12队列中得到验证。
基线TB是接受化疗免疫疗法的晚期NSCLC患者生存结果的预测性而非预后性临床生物标志物。TB评估与PD-L1状态评估相结合，可能会改善临床实践中一线化疗免疫疗法的患者分层，并为临床试验设计提供有价值的见解。
在线版本包含可在10.1186/s12885-025-14755-z获取的补充材料。
