Tumor Mutation Burden as a Potential Biomarker for PD-1/PD-L1 Inhibition in Advanced Non-small Cell Lung Cancer

被引:28
|
作者
Huang, Di [1 ,2 ]
Zhang, Fan [2 ]
Tao, Haitao [2 ]
Zhang, Sujie [2 ]
Ma, Junxun [2 ]
Wang, Jinliang [2 ]
Liu, Zhefeng [2 ]
Cui, Pengfei [2 ,3 ]
Chen, Shixue [2 ,3 ]
Huang, Ziwei [1 ,2 ]
Wu, Zhaozhen [1 ,2 ]
Zhao, Lei [2 ]
Hu, Yi [1 ,2 ]
机构
[1] Nankai Univ, Sch Med, 94 Weijin Rd, Tianjin 300071, Peoples R China
[2] Chinese Peoples Liberat Army Gen Hosp, Dept Med Oncol, 28 Fuxing Rd, Beijing 100853, Peoples R China
[3] Chinese Peoples Liberat Army Gen Hosp, Dept Grad Adm, Beijing, Peoples R China
基金
国家重点研发计划;
关键词
1ST-LINE TREATMENT; CTLA-4; BLOCKADE; STAGE IV; NIVOLUMAB; CHEMOTHERAPY; REARRANGEMENTS; PEMBROLIZUMAB; SENSITIVITY; LANDSCAPE; DOCETAXEL;
D O I
10.1007/s11523-020-00703-3
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Immunotherapy based on programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors has revolutionized the treatment of non-small cell lung cancer (NSCLC). Patients with high PD-L1 expression or DNA mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) cancer are reported to benefit from PD-1/PD-L1 inhibitors. However, additional biomarkers are needed, and whether tumor mutation burden (TMB) can be a robust biomarker or not is still controversial. Objective We conducted this study to assess TMB as a biomarker for PD-1/PD-L1 inhibitor treatment in advanced NSCLC patients in a real-world setting. Patients and Methods Chinese NSCLC patients who received a PD-1/PD-L1 inhibitor at the People's Liberation Army General Hospital and who had pathological tissues available for TMB were retrospectively analyzed. Demographic and clinical information were evaluated. Targeted next-generation sequencing (NGS) of the tumor tissue was performed. The relationship between TMB and clinical benefit was assessed. Results Thirty-four patients treated with PD-1/PD-L1 inhibitors between March 2015 and January 2019 were analyzed. The TMB was greater in patients with complete response (CR)/partial response (PR) versus stable disease (SD) versus progressive disease (PD) (median 11 vs. 9.7 vs. 4.2 mutations/megabase [Mb]; p = 0.049). The median progression-free survival was 10.6 months in the TMB-high group versus 3.9 months in the TMB-low group (cut-off value = 10 mutations/Mb) (hazard ratio [HR] 0.26 [95% confidence interval 0.12-0.57], p = 0.0007). The median overall survival was 21.0 months and 11.6 months (HR 0.37 [0.17-0.81], p = 0.0126) in the TMB-high group and the TMB-low group, respectively. The disease control rate was higher in the TMB-high group than in the TMB-low group (100% vs. 70%, p = 0.024). Conclusions High TMB was associated with a better outcome in advanced NSCLC patients who received PD-1/PD-L1 inhibitors in China. Further studies are needed to confirm our findings.
引用
收藏
页码:93 / 100
页数:8
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