Abstract 1614: The effect of tumor mutation burden on immune checkpoint inhibitors in non-small cell lung cancer

Backgroud: Tumor mutation burden (TMB) remains a promising but ambiguous biomarker for the efficacy of immune checkpoint inhibitors (ICIs)-based regimens. We conducted multifaceted systematic review and meta-analysis, and public cohort validation, to provide pooled evidence of the prediction value of TMB for ICIs in advanced non-small cell lung cancer (NSCLC). Methods: Mirror-based meta-analysis balancing the confounding factors was applied in Part1, and Bayesian network meta-analysis was conducted in Part2. PubMed, Embase, and Cochrane Central were searched and abstracts from conference were reviewed. All randomized controlled trials (RCTs) that investigated the predictive value of TMB in advanced NSCLC patients receiving ICIs were included. Baseline characteristics, hazard ratios (HRs) with 95% confidence intervals (95% CIs) for progression-free survival (PFS) and overall survival (OS) stratified by TMB status were extracted. Furthermore, public cohorts of advanced NSCLC treated with ICIs with genomic sequencing were analyzed in Part 3. Results: 10 RCTs covering 4443 patients and 5 public cohorts with 573 patients as validation were included. 9 RCTs were included in Part1a. TMB-high subgroup exhibited significantly superior PFS than TMB-low subgroup (HR 0.56, 95% CI 0.47-0.67) in NSCLC treated with ICIs compared with chemotherapy, and such superiority was consistent in the preplanned subgroup analysis based on the line of therapy, regimen modality, test method of TMB and PD-L1 expression. 7 RCTs were included in Part1b. No significant difference of PFS or OS was observed between anti-PD-L1 and anti-PD-1 according to TMB status. 7 RCTs were included in Part2. Among all first-line regimens in TMB-high group, platinum-based doublet chemotherapy combined with anti-PD-1 was most likely to rank first for PFS (probability of ranking best 48.29%, surface under the cumulative ranking curve 0.83), anti-PD-L1 plus anti-cytotoxic T-lymphocyte A antigen-4 (CTLA-4) provided the most favorable OS (63.89%, 0.86), and platinum-based chemotherapy ranked worst for PFS (0.03%, 0.11) and OS (0.02%, 0.09). In Part3, TMB was validated to be an independent predictor, which could further distinguish beneficiaries of ICIs in those with PD-L1 expression less than 50%. Conclusions: TMB could be used to identify beneficiaries of ICIs contained therapies and played a crucial role in determining the optimal first-line treatment among various available strategy for advanced NSCLC patients. Citation Format: Jie Zhao, Yiting Dong, Hua Bai, Jianchun Duan, Guoqiang Wang, Jiachen Xu, Zhijie Wang, Jie Wang. The effect of tumor mutation burden on immune checkpoint inhibitors in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1614.