Prospect of immunotherapy alone in patients with advanced NSCLC with high btmb: a review and a meta-analysis

Abstract

Lung cancer is the most prevalent cancer in the world, and the main treatment for advanced non-small cell lung cancer is immunotherapy combined with chemotherapy. In recent years, bTMB has received increasing attention as an emerging metric for monitoring the efficacy of tumour immunotherapy in terms of its operability, accessibility and real-time nature. We envisaged whether immunotherapy alone could be used to reduce the side effects of chemotherapy in patients with high bTMB lung cancer. We thus did a meta-analysis in order to show that immunotherapy alone is feasible in patients with high bTMB NSCLC.Methods This study aims to compare the efficacy of PD- 1/PD-L1 inhibitors (namely, atezolizumab, pembrolizumab, nivolumab, or tislelizumab) versus chemotherapy in NSCLC patients. The search for relevant studies was conducted in three major databases (i.e., PubMed, Embase, and Medline) up until January 2023. Specifically, we identified studies that reported risk ratios (HRs) for reporting progression-free survival (PFS) or overall survival (OS), or objective remission rates (ORs) for immunotherapy alone versus chemotherapy in high bTMB and low bTMB patient groups. Given that NSCLC represents the predominant type of lung cancer, we exclusively focused on this subtype. Our analysis encompassed a meta-analysis of the identified literature, incorporating heterogeneity analysis and sensitivity analysis. The quality of the evidence is evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to ascertain the reliability and robustness of the findings.Result-We conducted a meta-analysis of seven randomised controlled trials including 4,755 patients with advanced non-small cell lung cancer (NSCLC) evaluated the efficacy of PD- 1 or PD-L1 monotherapy compared to chemotherapy alone. All patients were randomized to receive either PD- 1/PD-L1 treatment alone or chemotherapy alone as a control. In the high bTMB patient group, PD- 1/PD-L1 monotherapy resulted in significant improvements in overall survival (HR = 0.55, 95% CI 0.49–0.61, p = 0.77) and progression-free survival (HR = 0.74, 95% CI 0.68–0.81, p = 0.78) compared to chemotherapy alone. Conversely, in the low bTMB patient group, PD- 1 monotherapy or PD-L1 monotherapy failed to demonstrate significant improvements in overall survival (HR = 0.82, 95% CI 0.73–0.92, p = 0. 13) and progression-free survival (HR = 1.22, 95% CI 1.22- 1.45, p = 0.003) in advanced NSCLC. Conclusion Our analysis suggests that monotherapy with immunotherapy is a feasible option for patients with advanced NSCLC and high bTMB. However, the results have to be construed with caution because of the small sample size and the potential bias in the studies included. Therefore, further research with larger sample sizes and rigorous study designs is necessary to confirm the observed benefits of immunotherapy in this patient population.