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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 6604-6622 |
| Number of pages | 19 |
| Journal | Oncotarget |
| Volume | 10 |
| Issue number | 61 |
| DOIs | |
| State | Published - 2019 |
Bibliographical note
Funding Information:This study was sponsored by Bristol-Myers Squibb. Medical writing assistance was provided by Martin Bell, PhD, of Evidence Medical Affairs, and was funded by Bristol-Myers Squibb. The authors wish to acknowledge Komal Singh, Gabriel Krigsfeld, Signe Fransen, and Lisa Siegartel for their assistance in conducting and providing feedback on this systematic literature review. Michelle Fiander was an employee of the Department of Pharmacotherapy, University of Utah, UT at the time of initiation of the review. BMS policy on data sharing may be found at https://www.bms.com/researchers-and-partners/independent-research/data-sharing-request-process.html.
Publisher Copyright:
Willis et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords
- Biomarkers
- Chemotherapy
- Immunotherapy
- Lung cancer
- PD-L1
