免疫检查点抑制剂在具有罕见突变的晚期非小细胞肺癌患者中的疗效：一项真实世界回顾性研究。
Efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer patients with rare mutations: a real-world retrospective study.
作者信息
Jiang Haohua, Li Yujing, Wang Yanan, Zou Benkun, Chen Ya, Zhang Yanwei, Husain Hatim, Forest Fabien, Qian Fangfei, Zhang Lele, Zhou Chao, Liu Hongyu, Wang Danni, Zhang Wei, Lu Jun, Han Baohui
机构信息
Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Medical Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China.
出版信息
Transl Lung Cancer Res. 2024 Jul 30;13(7):1672-1684. doi: 10.21037/tlcr-24-372. Epub 2024 Jul 25.
BACKGROUND
Kirsten rat sarcoma homolog () mutations are one of the key drivers in non-small cell lung cancer (NSCLC) and FDA-approved specific inhibitors of -G12C mutation are available clinically. However, inhibitors of certain KRAS mutation subtypes remain unavailable, especially rare mutations including G13C, G13D, and Q61H. In this study, we retrospectively investigated the outcomes of NSCLC patients with rare -mutation to determine if they may benefit from immune checkpoint inhibitors (ICIs).
METHODS
Our retrospective study involved 240 advanced NSCLC patients with mutations, who visited Shanghai Chest Hospital from July 2018 to July 2021. Complete clinical and pathological data were recorded and progression-free survival (PFS) and overall survival (OS) were adopted as primary endpoints.
RESULTS
The median follow-up time was 36.5 months (range, 30.8-42.1 months) and the median OS was 9.7 months (range, 7.6-11.8 months). Of the 240 patients evaluated, 130 (54.2%) received chemotherapy and 110 (45.8%) received ICI-based treatment. Among the patients who received chemotherapy, patients with rare -mutations presented worse survival outcomes (median PFS, 3.4 4.1 months, P=0.047; median OS, 5.2 7.1 months, P=0.02) than conventional -mutant patients. PFS and OS of rare -mutation patients were prolonged after immunotherapy (median PFS 7.3 3.4 months, P<0.001; median OS, 13.3 5.2 months, P<0.001) and had no significant difference compared with conventional -mutant patients, in part of them whose programmed death-ligand 1 (PD-L1) expression data before immunotherapy were available (n=72), patients with a higher rate of PD-L1 positive tumor cells (≥50%) presented elevated PFS and OS.
CONCLUSIONS
Despite having potential survival disadvantage compared with other NSCLC patients, rare KRAS-mutant patients (other than G12A, C, D, V) could benefit specifically from ICI-based therapy and survival outcomes are correlated with PD-L1 expression.
背景
Kirsten大鼠肉瘤同源物（KRAS）突变是非小细胞肺癌（NSCLC）的关键驱动因素之一，美国食品药品监督管理局（FDA）批准的针对KRAS - G12C突变的特异性抑制剂已在临床上可用。然而，某些KRAS突变亚型的抑制剂仍然无法获得，尤其是罕见的突变，包括G13C、G13D和Q61H。在本研究中，我们回顾性调查了具有罕见KRAS突变的NSCLC患者的预后，以确定他们是否可能从免疫检查点抑制剂（ICI）中获益。
方法
我们的回顾性研究纳入了240例2018年7月至2021年7月期间就诊于上海胸科医院的晚期NSCLC患者，这些患者具有KRAS突变。记录完整的临床和病理数据，并将无进展生存期（PFS）和总生存期（OS）作为主要终点。
结果
中位随访时间为36.5个月（范围30.8 - 42.1个月），中位OS为9.7个月（范围7.6 - 11.8个月）。在评估的240例患者中，130例（54.2%）接受了化疗，110例（45.8%）接受了基于ICI的治疗。在接受化疗的患者中，具有罕见KRAS突变的患者的生存结果（中位PFS，3.4对4.1个月，P = 0.047；中位OS，5.2对7.1个月，P = 0.02）比传统KRAS突变患者更差。免疫治疗后，罕见KRAS突变患者的PFS和OS延长（中位PFS 7.3对3.4个月，P < 0.001；中位OS，13.3对5.2个月，P < 0.001），与传统KRAS突变患者相比无显著差异，其中部分患者有免疫治疗前程序性死亡配体1（PD - L1）表达数据（n = 72），PD - L1阳性肿瘤细胞率较高（≥50%）的患者PFS和OS升高。
结论
尽管与其他NSCLC患者相比存在潜在的生存劣势，但罕见KRAS突变患者（除G12A、C、D、V外）可从基于ICI的治疗中特别获益，且生存结果与PD - L1表达相关。
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