The association of efficacy with PD-1/PD-L1 inhibition and tumor mutational burden in advanced nonsmall cell lung cancer: A PRISMA-guided literature review and meta-analysis

Abstract

Background: Tumor mutation burden (TMB) has been reported to emerge as an independent biomarker of response to identify patients who would achieve benefit from immune checkpoint inhibitors. However, it still remains controversy that whether TMB can be a robust biomarker of response to programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibition. We performed this meta-analysis to assess the relationship between TMB and the efficacy with PD-1/PD-L1 inhibition in advanced nonsmall cell lung cancer (NSCLC). Methods: Following the recommendations of the PRISMA statement, electronic databases literature search was done on the published articles till March 2021, including Pubmed, Embase, and Cochrane library databases. Studies were selected that focused on comparing the efficacy of TMB-high group and TMB-low group in NSCLC patients received with immune checkpoint inhibitors. Meta-analysis Revman 5.3 software was utilized to calculate the pooled outcomes. Results: A systematic literature search was conducted 8 articles, including 11 comparative articles. Findings of our studies shown that patients with TMB-high group was associated with better clinical outcomes than TMB-low group, including progression-free survival (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.29–0.49; P < .00001), complete response (OR, 4.71; 95% CI, 2.32–9.57; P < .0001), durable clinical benefit (OR, 3.76; 95% CI, 2.38–5.96; P < .00001) and the objective response rate (OR, 3.14; 95% CI, 1.83–5.37; P < .0001). While, it failed to predict overall survival benefits (OR, 0.74; 95% CI, 0.45–1.20; P = .22). Conclusions: Our study found that NSCLC with high TMB who benefit from immunotherapy. The findings suggest that TMB could associated with a greater predictive power of response. Possibly a more TMB-oriented prediction model might gain more benefits from PD-1/PD-L1 inhibitors.

The correlation between the influencing factors and efficacy of immune checkpoint inhibitor therapy: an umbrella meta-analysis of randomized controlled trials

“…Compared with patients with low TMB, patients with high TMB acquired more benefits from ICI therapy (PFS: 0.42, 0.34 to 0.51, p < .001), supported by strong evidence, respectively ( Table 1 and Supplementary Figures 13 and 14). The high TMB status may be related to the increase in the production and presentation of effective neoantigens, which greatly enhance the anti-tumour response [ 28 , 29 ].…”

A Prognostic Model for Predicting Liver Cancer Patients Based On Immune Checkpoint Gene-Related Basement Membrane Genes, And Analyzing Immunity and Potential Drug Candidates

“…Tumor mutational load, which is the total number of somatic or acquired mutations per million bases in a particular area of the tumor genome, and transcriptome expression both have prognostic significance in patients receiving immune checkpoint inhibitor therapy for colon cancer 16,17 . A possible biomarker for immunotherapy susceptibility and prognosis in patients with lowgrade gliomas has also been identified as tum-our mutational burden [18][19][20] . According to the findings of this study's survival analysis of tumour mutational burden, high tumour mutational burden groups' patients had a noticeably inferior survival rate as compare to the patients in the low tumour mutational burden group.…”