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

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

doi:10.3389/fphar.2019.00673

Abstract

Background: 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. Methods: 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. Results: 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; P = 0.004] and 0.73 (95% CI 0.50 to 1.08; P = 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; P = 0.229) and 1.00 (95% CI 0.80 to 1.24; P = 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; P = 0.000). Patients with high TMB showed significant benefits from PD-1/PD-L1 inhibitions compared to patients with low TMB. Conclusion: Despite the present technical and practical barriers, TMB may be a preferable biomarker to optimize the efficacy of PD-1/PD-L1 inhibitions.

Highlights

Cancer is a serious health problem and is the major leading cause of death worldwide (Torre et al, 2015)
Comparing patients with high Tumor mutation burden (TMB) to patients with low TMB, the pooled hazard ratios (HR) for progression-free survival (PFS) in patients treated with programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitions was 0.47
The analysis showed that patients with high TMB had significant benefits on PFS compared to patients with low TMB when they were treated with PD-1/PD-L1 inhibitions

Summary

Introduction

Cancer is a serious health problem and is the major leading cause of death worldwide (Torre et al, 2015). It was shown that the 5-year survival rate for all tumor patients is only 67% (Tong et al, 2018). The programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitions are the representative treatments involving immunotherapy. Many studies have shown that PD-1/PD-L1 inhibitions could improve outcomes of cancer patients compared to chemotherapy (Borghaei et al, 2015; Herbst et al, 2016; Rittmeyer et al, 2017). The efficacy of PD-1/PD-L1 inhibitions varies from individual. Researchers are exploring some biomarkers to assess the efficacy of PD-1/PD-L1 inhibitions. Programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PDL1) inhibitions are being strongly recommended for the treatment of various cancers, while the efficacy of PD-1/PD-L1 inhibitions varies from individuals. We conducted a meta-analysis to quantitatively explore the association between TMB and outcomes of PD-1/PD-L1 inhibitions

Methods

Results

Discussion

Conclusion