Abstract 686P
Background
To date, immune checkpoint inhibitors (ICIs) have become the mainstay of treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) while a subset of patients derive poor benefits from ICIs. Biomarkers analysis is in great need to select patients who will respond to ICIs. In view of the controversy concerning the efficacy of tumor mutational burden (TMB) for ICIs in NSCLC, we performed a meta-analysis using recently published randomized clinical trials to explore the value of TMB in NSCLC treated with ICIs.
Methods
PubMed, Embase, Web of Science, and Cochrane Library were systematically searched from inception to April 2, 2024, and no language limitation was applied. The end points were overall response rate (ORR), overall survival (OS), and progression-free survival (PFS). A meta-analysis was carried out with Review Manager 5.4.
Results
A total of 13 randomized controlled trials were included. High TMB was associated with better ORR [relative ratio (RR) 1.63, 95 % confidence interval (CI) 1.24–2.14], longer PFS [hazard ratio (HR) 0.78, 95 % CI 0.71–0.86] and OS (HR 0.86, 95 % CI 0.76–0.98). Based on the subgroup analysis, high tissue TMB (tTMB) was associated with improved PFS (HR 0.69, 95% CI 0.60-0.78) and OS (HR 0.79, 95% CI 0.67-0.93), while the pooled results of both PFS (HR 0.91, 95% CI 0.79-1.04) and OS (HR 0.96, 95% CI 0.81-1.12) of blood TMB (bTMB) did not achieve statistical significance. In the high TMB group, there was a significant benefit for NSCLC when treated with first-line ICIs according to the analysis of ORR, PFS and OS. The association with survival was not statistically significant in second- or later-line ICIs treatment group, with an HR of 0.91 for OS (95 % CI 0.73–1.13) and 0.90 for PFS (95 % CI 0.73–1.10).
Conclusions
This study found that NSCLC with high TMB benefit more from ICIs and the further analysis of tTMB subgroup had statistical significance. These results suggest that tTMB could be used as a potential predictor of clinical benefit from ICIs, especially for the previously untreated NSCLC. However, the predictive value of bTMB requires further investigation and definition of bTMB cutpoint remains challenging.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.