Liu Hui, Hong Qiyuan, Zheng Shuohan, Zhang Meifang, Cai Ling
Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China; State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China.
Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China; Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou 510060, PR China.
Lung Cancer. 2024 Dec;198:108022. doi: 10.1016/j.lungcan.2024.108022. Epub 2024 Nov 9.
SMARCA4/BRG1-deficient non-small cell lung cancer (SD-NSCLC) with high invasiveness and poor prognosis is associated with primary resistance to standard treatment, especially in late-stage patients. This study aimed to explore effective treatments and identify critical factors impacting therapeutic efficacy to enhance outcomes for SD-NSCLC patients.
103 SD-NSCLC patients in stage III/IV diagnosed by immunohistochemistry from May 2019 to March 2024 were included in this study. We assessed the patients' clinical and genetic features, analyzed the clinical outcomes of local treatment and immunotherapy according to the TNM stage, and further evaluated the factors impacting therapeutic efficacy.
In stage III patients, no significant differences in the median progression-free survival (mPFS) and median overall survival (mOS) were observed between patients receiving local treatment at the primary site and those who did not (p > 0.05), while adding ICIs (immune checkpoint inhibitors) to local treatment significantly improved mPFS compared with non-ICIs (15.0 vs. 7.7 months, p = 0.033), though not mOS (p > 0.05). For stage IV patients, ICIs significantly improved mPFS (8.9 vs. 4.2 months, p = 0.006) and mOS (19.7 vs. 13.1 months, p = 0.007) compared to non-ICIs treatments. However, among ICIs-treated patients, the addition of local treatment to the primary lesion did not significantly affect mPFS and mOS (p > 0.05). Patients with STK11/KEAP1 mutations had significantly shorter mPFS (3.6 vs. 16.2 months, p = 0.001) and mOS (17.7 vs. 31.3 months, p = 0.002), while no significant difference was observed in mPFS and mOS in patients with different tumor mutation burden (TMB) and PD-L1 expression levels.
The addition of ICIs to local treatment shows promising results for locally advanced patients with SD-NSCLC, and first-line ICIs are associated with improved survival in metastatic SD-NSCLC. STK11/KEAP1 mutations may be linked to reduced efficacy of immunotherapy.
SMARCA4/BRG1缺陷型非小细胞肺癌（SD-NSCLC）具有高侵袭性和不良预后，与对标准治疗的原发性耐药相关，尤其是在晚期患者中。本研究旨在探索有效的治疗方法，并确定影响治疗效果的关键因素，以改善SD-NSCLC患者的预后。
本研究纳入了2019年5月至2024年3月通过免疫组织化学诊断为III/IV期的103例SD-NSCLC患者。我们评估了患者的临床和基因特征，根据TNM分期分析了局部治疗和免疫治疗的临床结局，并进一步评估了影响治疗效果的因素。
在III期患者中，接受原发部位局部治疗的患者与未接受局部治疗的患者之间，中位无进展生存期（mPFS）和中位总生存期（mOS）无显著差异（p>0.05），而在局部治疗中添加免疫检查点抑制剂（ICIs）与未添加ICIs相比，显著改善了mPFS（15.0个月对7.7个月，p=0.033），但mOS无显著改善（p>0.05）。对于IV期患者，与非ICIs治疗相比，ICIs显著改善了mPFS（8.9个月对4.2个月，p=0.006）和mOS（19.7个月对13.1个月，p=0.007）。然而，在接受ICIs治疗的患者中，对原发灶添加局部治疗并未显著影响mPFS和mOS（p>0.05）。STK11/KEAP1突变的患者mPFS（3.6个月对16.2个月，p=0.001）和mOS（17.7个月对31.3个月，p=0.002）显著缩短，而不同肿瘤突变负荷（TMB）和PD-L1表达水平的患者在mPFS和mOS上未观察到显著差异。
在局部治疗中添加ICIs对局部晚期SD-NSCLC患者显示出有希望的结果，一线ICIs与转移性SD-NSCLC患者生存率的提高相关。STK11/KEAP1突变可能与免疫治疗疗效降低有关。
