Abstract
Purpose: To assess the association of tumor mutational burden (TMB) with clinical outcomes, other biomarkers and patient/disease characteristics in patients receiving therapy for lung cancer. Results: In total, 4,303 publications were identified; 81 publications were included. The majority of publications assessing clinical efficacy of immunotherapy reported an association with high TMB, particularly when assessing progression-free survival and objective response rate. High TMB was consistently associated with TP53 alterations, and negatively associated with EGFR mutations. High TMB was also associated with smoking, squamous cell non-small cell lung carcinoma, and being male. Methods: A systematic literature review based upon an a priori protocol was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane methodologies. Searches were conducted in EMBASE, SCOPUS, Ovid MEDLINE®, and Emcare (from January 2012 until April 2018) and in two clinical trial registries. Conference abstracts were identified in EMBASE, and in targeted searches of recent major conference proceedings (from January 2016 until April 2018). Publications reporting data in patients receiving therapy for lung cancer that reported TMB and its association with clinical efficacy, or with other biomarkers or patient/disease characteristics, were included. Results are presented descriptively. Conclusion: This systematic literature review identified several clinical outcomes, biomarkers, and patient/disease characteristics associated with high TMB, and highlights the need for standardized definitions and testing practices. Further studies using standardized methodology are required to inform treatment decisions.
Highlights
The advent of immunotherapy has transformed the clinical oncology landscape in recent years, with significant improvements in long-term survival in some patients
This systematic literature review identified several clinical outcomes, biomarkers, and patient/disease characteristics associated with high tumor mutational burden (TMB), and highlights the need for standardized definitions and testing practices
A summary of relevant data reported by publications presenting efficacy outcomes, biomarkers and/or patient or disease characteristics is presented in Supplementary Table 4
Summary
The advent of immunotherapy has transformed the clinical oncology landscape in recent years, with significant improvements in long-term survival in some patients. A large proportion of patients do not respond to immunotherapies, and predictors of response are required to improve patient selection. Tumor mutational burden (TMB) has recently emerged as a potential predictor of response to immunotherapy in various tumor types [1, 2]. Tumors with high levels of TMB are thought to express more cancer-specific antigens (neoantigens) that may sensitize them to immunotherapy [1, 5,6,7]. TMB levels have been shown to correlate with objective response rates (ORR) during immunotherapy across a number of cancer types [8]
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