Tumor mutational burden in lung cancer: a systematic literature review

Connor Willis, Michelle Fiander, Dao Tran, Beata Korytowsky, John-Michael Thomas, Florencio Calderon, Teresa M. Zyczynski, Diana Brixner and David D. Stenehjem _

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Oncotarget. 2019; 10:6604-6622. https://doi.org/10.18632/oncotarget.27287

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Connor Willis1, Michelle Fiander1, Dao Tran2, Beata Korytowsky3, John-Michael Thomas3, Florencio Calderon3, Teresa M. Zyczynski3, Diana Brixner1 and David D. Stenehjem1,2

1 Department of Pharmacotherapy, University of Utah, Salt Lake City, UT, USA

2 Department of Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota, Duluth, MN, USA

3 Bristol-Myers Squibb Company, Lawrenceville, NJ, USA

Correspondence to:

David Stenehjem,email: stene032@d.umn.edu

Keywords: biomarkers; chemotherapy; immunotherapy; lung cancer; PD-L1

Received: June 14, 2019     Accepted: September 16, 2019     Published: November 12, 2019


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.

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