Real-world survival analysis by tumor mutational burden in non-small cell lung cancer: a multisite U.S. study
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Connor Willis1, Hillevi Bauer1, Trang H. Au1, Jyothi Menon1, Sudhir Unni1, Dao Tran2, Zachary Rivers2, Wallace Akerley3, Matthew B. Schabath4, Firas Badin5, Ashley Sekhon6, Malini Patel7, Bing Xia8, Beth Gustafson9, John L. Villano10, John-Michael Thomas11, Solomon J. Lubinga12, Michael A. Cantrell13, Diana Brixner1 and David Stenehjem1,2
1 Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT, USA
2 Department of Pharmacy Practice and Pharmaceutical Sciences, College of Pharmacy, University of Minnesota, Duluth, MN, USA
3 Department of Internal Medicine, Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT, USA
4 Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
5 Department of Hematology and Oncology, Baptist Health Medical Group, Lexington, KY, USA
6 Department of Radiation Oncology, MetroHealth Medical Center, Cleveland, OH, USA
7 Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
8 Department of Medicine, Kenneth Norris Jr. Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA
9 Precision Oncology Program, Saint Luke’s Cancer Institute, Kansas City, MO, USA
10 Department of Internal Medicine, Markey Cancer Center, University of Kentucky, Lexington, KY, USA
11 US Medical Oncology, Bristol Myers Squibb, Princeton, NJ, USA
12 Health Economics and Outcomes Research, Bristol Myers Squibb, Princeton, NJ, USA
13 Global Medical Oncology, Bristol Myers Squibb, Princeton, NJ, USA
Keywords: lung neoplasma; tumor biomarkers; immunotherapy
Received: September 15, 2021 Accepted: December 24, 2021 Published: January 31, 2022
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.
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