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Predictive value of tumor mutational burden for immunotherapy in non-small cell lung cancer: A systematic review and meta-analysis

BACKGROUND: Immunotherapy has emerged as a promising treatment for non-small cell lung cancer (NSCLC). Yet, some patients cannot benefit from immunotherapy, and reliable biomarkers for selecting sensitive patients are needed. Herein, we performed a meta-analysis to evaluate the predictive value of t...

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Detalles Bibliográficos
Autores principales: Meng, Guangxian, Liu, Xiaowei, Ma, Tian, Lv, Desheng, Sun, Ge
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8812984/
https://www.ncbi.nlm.nih.gov/pubmed/35113949
http://dx.doi.org/10.1371/journal.pone.0263629
Descripción
Sumario:BACKGROUND: Immunotherapy has emerged as a promising treatment for non-small cell lung cancer (NSCLC). Yet, some patients cannot benefit from immunotherapy, and reliable biomarkers for selecting sensitive patients are needed. Herein, we performed a meta-analysis to evaluate the predictive value of tumor mutational burden (TMB) in NSCLC patients treated with immunotherapy. METHODS: Eligible studies were comprehensively searched from electronic databases prior to August 31, 2021. Meta-analyses of high TMB versus low TMB as well as immunotherapy versus chemotherapy in patients with high/low TMB were conducted. Hazard ratio (HR) with corresponding 95% confidence interval (95%CI) for progression-free survival (PFS) and overall survival (OS) and odds ratio (OR) with 95%CI for objective response rate (ORR) were calculated. RESULTS: A total of 31 datasets (3437 patients) and 6 randomized controlled trials (3662 patients) were available for meta-analyses of high TMB versus low TMB and immunotherapy versus chemotherapy, respectively. High TMB predicted significantly favorable PFS (HR = 0.54, 95%CI: 0.46–0.63, P<0.001) and OS (HR = 0.70, 95%CI: 0.57–0.87, P = 0.001), and higher ORR (OR = 3.14, 95%CI: 2.28–4.34, P<0.001) compared with low TMB. In patients with high TMB, immunotherapy was associated with improved PFS (HR = 0.62, 95%CI: 0.53–0.72), OS (HR = 0.67, 95%CI: 0.57–0.79) and ORR (OR = 2.35, 95%CI: 1.74–3.18) when compared with chemotherapy. However, in patients with low TMB, immunotherapy seemed to predict inferior PFS (HR = 1.20, 95%CI: 1.02–1.41) and ORR (OR = 0.61, 95%CI: 0.44–0.84) and have no OS benefit (HR = 0.88, 95%CI: 0.74–1.05) as compared with chemotherapy. CONCLUSION: This meta-analysis demonstrates more clinical benefits concerning treatment response and survival outcomes in high-TMB NSCLC patients who are treated with immunotherapy. TMB is a promising biomarker for discriminating NSCLC patients who can benefit more from immunotherapy.