Li Qianni, Zhou Qi, Zhao Shicai, Wu Peng, Shi Ping, Zeng Jia, Xiong Xiaomin, Chen Haiwen, Kittaneh Muaiad, Bravaccini Sara, Zanoni Michele, Zhou Chengzhi, Zhang Jiexia
Department of Respiratory Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Respiratory Medicine, Guangyuan Central Hospital, Guangyuan, China.
Transl Lung Cancer Res. 2022 Oct;11(10):2136-2147. doi: 10.21037/tlcr-22-655.
The selection of patients for immunotherapy remains challenging given the lack of highly specific and highly sensitive biomarkers. Kirsten rat sarcoma () mutation is the most frequent molecular alteration found in advanced non-small cell lung carcinoma (NSCLC). We explored whether mutation status predicted the effects of first-line immune checkpoint inhibitor (ICI) treatment and platinum-based chemotherapy in Chinese patients with advanced NSCLC.
Clinical data were extracted from medical records of patients with advanced NSCLC at the First Affiliated Hospital of Guangzhou Medical University in China between January 2019 and March 2020. Overall survival (OS) and progression-free survival (PFS) rates were compared via log-rank tests, and independent prognostic factors were identified via Cox regression.
Patients with advanced NSCLC without driver alterations who were treated with ICI and platinum-based chemotherapy (N=80) were identified, including 28.7% with mutations and 71.3% with non- mutations. Tumor programmed death-ligand 1 (PD-L1) expression was analyzed using a 1% cutoff, and 32.5% of patients were negative and 67.5% were positive. The median tumor mutational burden (TMB) was 7.29 mutations per megabase (muts/Mb) (range, 0.08-44.8 muts/Mb), with 32.5% of cases <5 muts/Mb and 67.5% ≥5 muts/Mb. The median PFS and OS for the entire cohort were 9.8 (95% CI: 9.1-10.5) and 17.6 (95% CI: 14.4-20.8) months, respectively. The 6-month PFS rate was 67.5% and the 1-year OS rate was 72.5%. Thirty-five patients survived until the last follow-up. The OS and PFS of patients with KRAS mutations were significantly higher than those in the non-KRAS mutant group (P<0.05). The Cox multivariate analyses showed that brain metastasis [hazard ratio (HR) =0.232, 95% CI: 0.102-0.530; P=0.001], TMB (HR =5.675, 95% CI: 1.948-16.535; P=0.001), mutation (HR =2.552, 95% CI: 1.141-5.708; P=0.023) were independent predictors of OS in patients treated with ICIs and platinum-based chemotherapy. Liver metastasis (HR =0.344, 95% CI: 0.191-0.619; P<0.001) and /tumor protein p53 () co-mutation (HR =0.220, 95% CI: 0.067-0.725; P=0.013) were the prognostic factor for PFS of qualified patients.
This work provides evidence that mutation in advanced NSCLC may be served as a potential predictive biomarker for immunotherapeutic efficacy.
鉴于缺乏高度特异性和高敏感性的生物标志物，免疫治疗患者的选择仍然具有挑战性。 Kirsten大鼠肉瘤（KRAS）突变是晚期非小细胞肺癌（NSCLC）中最常见的分子改变。我们探讨了KRAS突变状态是否可预测中国晚期NSCLC患者一线免疫检查点抑制剂（ICI）治疗和铂类化疗的疗效。
从2019年1月至2020年3月在中国广州医科大学附属第一医院的晚期NSCLC患者的病历中提取临床数据。通过对数秩检验比较总生存期（OS）和无进展生存期（PFS）率，并通过Cox回归确定独立预后因素。
确定了接受ICI和铂类化疗的无驱动改变的晚期NSCLC患者（N = 80），其中28.7% 有KRAS突变，71.3% 无KRAS突变。使用1% 的临界值分析肿瘤程序性死亡配体1（PD-L1）表达，32.5% 的患者为阴性，67.5% 为阳性。肿瘤突变负荷（TMB）中位数为每兆碱基7.29个突变（muts/Mb）（范围：0.08 - 44.8 muts/Mb），32.5% 的病例<5 muts/Mb，67.5% ≥5 muts/Mb。整个队列的中位PFS和OS分别为9.8（95% CI：9.1 - 10.5）个月和17.6（95% CI：14.4 - 20.）个月。6个月PFS率为67.5%，1年OS率为72.5%。35例患者存活至最后一次随访。KRAS突变患者的OS和PFS显著高于非KRAS突变组（P<0.05）。Cox多因素分析显示，脑转移[风险比（HR）=0.232，95% CI：0.102 - 0.530；P = 0.001]、TMB（HR = 5.675，95% CI：1.948 - 16.535；P = 0.001）、KRAS突变（HR = 2.552，95% CI：1.141 - 5.708；P = 0.0）是接受ICI和铂类化疗患者OS的独立预测因素。肝转移（HR = 0.344，95% CI：0.191 - 0.619；P<0.001）和KRAS/肿瘤蛋白p53（TP53）共突变（HR = 0.220，95% CI：0.067 - 0.725；P = 0.013）是合格患者PFS的预后因素。
这项研究提供了证据，表明晚期NSCLC中的KRAS突变可能作为免疫治疗疗效的潜在预测生物标志物。
