AUTHOR=Zhu Jiaxin , Zhang Tiantian , Li Jiahao , Lin Junming , Liang Wenhua , Huang Wenjie , Wan Ning , Jiang Jie 

TITLE=Association Between Tumor Mutation Burden (TMB) and Outcomes of Cancer Patients Treated With PD-1/PD-L1 Inhibitions: A Meta-Analysis

JOURNAL=Frontiers in Pharmacology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.00673

DOI=10.3389/fphar.2019.00673

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitions are being strongly recommended for the treatment of various cancers, while the efficacy of PD-1/PD-L1 inhibitions varies from individuals. It is urgent to explore some biomarkers to screen the most appropriate cancer patients. Tumor mutation burden (TMB) as a potential alternative has been drawing more and more attention. Therefore, we conducted a meta-analysis to quantitatively explore the association between TMB and outcomes of PD-1/PD-L1 inhibitions.</p><p><bold>Methods:</bold> We searched eligible studies that evaluated the association between TMB and the outcomes of PD-1/PD-L1 inhibitions from PubMed, Embase, and Cochrane database up to October 2018. The primary endpoints were the progression-free survival (PFS) and the overall survival (OS) in patients with high TMB or low TMB. The pooled hazard ratios (HR) for PFS and OS were performed by Stata.</p><p><bold>Results:</bold> In this analysis, a total of 2,661 patients from eight studies were included. Comparing PD-1/PD-L1 inhibitions to chemotherapy, the pooled HR for PFS and OS in patients with high TMB was 0.66 [95% confidence interval (CI) 0.50 to 0.88; <italic>P</italic> = 0.004] and 0.73 (95% CI 0.50 to 1.08; <italic>P</italic> = 0.114), respectively, while the pooled HR for PFS and OS in patients with low TMB was 1.38 (95% CI 0.82 to 2.31; <italic>P</italic> = 0.229) and 1.00 (95% CI 0.80 to 1.24; <italic>P</italic> = 0.970), respectively. Meanwhile, comparing patients with high TMB to patients with low TMB, the pooled HR for PFS in patients treated with PD-1/PD-L1 inhibitions was 0.47 (95% CI 0.35 to 0.63; <italic>P</italic> = 0.000). Patients with high TMB showed significant benefits from PD-1/PD-L1 inhibitions compared to patients with low TMB.</p><p><bold>Conclusion:</bold> Despite the present technical and practical barriers, TMB may be a preferable biomarker to optimize the efficacy of PD-1/PD-L1 inhibitions.</p>