Real-world survival analysis by tumor mutational burden in non-small cell lung cancer: A multisite U.S. study

Connor Willis, Hillevi Bauer, Trang H. Au, Jyothi Menon, Sudhir Unni, Dao Tran, Zachary Rivers, Wallace Akerley, Matthew B. Schabath, Firas Badin, Ashley Sekhon, Malini Patel, Bing Xia, Beth Gustafson, John L. Villano, John Michael Thomas, Solomon J. Lubinga, Michael A. Cantrell, Diana Brixner, David Stenehjem

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Tumor mutational burden (TMB) is a potential biomarker to predict tumor response to immuno-oncology agents in patients with metastatic non-small cell lung cancer (NSCLC). Materials and Methods: A multi-site cohort study evaluated patients diagnosed with stage IV NSCLC between 2012 and 2019 who had received comprehensive genomic profiling (CGP) and any NSCLC-related treatment at 9 U.S. cancer centers. Baseline characteristics and clinical outcomes were compared between patients with TMB <10 and TMB ≥10. Results: Among the 667 patients with CGP results, most patients received CGP from Foundation Medicine (64%) or Caris (20%). Patients with TMB ≥10 (vs. TMB <10) were associated with a positive smoking history. TMB was associated with ALK (p = 0.01), EGFR (p < 0.01), and TP53 (p < 0.05) alterations. TMB >10 showed a significant association towards longer overall survival (OS) (HR: 0.43, 95% CI: 0.21. 0.88, p = 0.02) and progression-free survival (PFS) (HR: 0.43, 95% CI: 0.21.0.85, p = 0.02) in patients treated with first-line immunotherapy and tested by Foundation Medicine or Caris at treatment initiation. Conclusions: TMB levels greater than or equal to 10 mut/Mb, when tested by Foundation Medicine or Caris at treatment initiation, were significantly associated with improved OS and PFS among patients treated with first-line immunotherapy containing regimens. Additional prospective research is warranted to validate this biomarker along with PD-L1 expression.

Original languageEnglish
Pages (from-to)257-270
Number of pages14
JournalOncotarget
Volume13
DOIs
StatePublished - Jan 31 2022

Bibliographical note

Funding Information:
We thank the Oncology Research Information Exchange Network (ORIEN) sites for their participation in this study. We also thank Howard Colman, MD, PhD, FAAN, of the Huntsman Cancer Institute and Department of Neurology at the University of Utah as the liaison with the ORIEN sites and Mikaela Larson at Huntsman Cancer Institute for her assistance with ORIEN sites management. We also thank Kelley Lindberg of Blue Raven Services, Inc., for her contributions in drafting the manuscript. The research reported in this publication was supported in part by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR002538, as well as Award Numbers UL1TR002494 and TL1R002493. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Funding Information:
University of Utah authors CW, HB, THA, JM, SU, WA, DB, and DS received research funding from BMS for their institution for the work under consideration. Site primary investigators MBS, FB, AS, MP, BX, BG, and JLV received payments to their institutions for research time dedicated to this project. JMT, SJL, MC as employees of BMS received compensation from their employer for participation in this study and in preparation of the manuscript. WA has declared research funding from Astra Zeneca. FB has declared consulting fees from BMS and payments by BMS from the speaking bureau. MP has declared payment from Bayer for presentations. DS has declared consulting fees from BMS.

Funding Information:
This research was support by Bristol-Myers Squibb under contract with the Pharmacotherapy Outcomes Research Center at the University of Utah.

Publisher Copyright:
© 2022 Willis et al.

Keywords

  • Immunotherapy
  • Lung neoplasma
  • Tumor biomarkers

ASJC Scopus subject areas

  • Oncology

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