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.
Highlights
Immune checkpoint inhibitors (ICIs) have substantially improved the clinical outcomes of some patients with metastatic non-small cell lung cancer (NSCLC) [1,2,3,4]
Sites were categorized by region, with the West region comprised of University of Washington, Huntsman Cancer Institute, and Kenneth Norris Jr
When assessing overall survival (OS) by Tumor mutational burden (TMB) in patients with TMB testing within 60 days of treatment initiation the association became statistically significant. These results suggest an association between higher TMB and increased OS, with the greatest predictive value when TMB is assessed at treatment initiation, possibly due to TMB changes with time and treatment
Summary
Immune checkpoint inhibitors (ICIs) have substantially improved the clinical outcomes of some patients with metastatic non-small cell lung cancer (NSCLC) [1,2,3,4]. Previous research has shown inconsistent results regarding the ability of PD-L1 expression to predict treatment response [2, 7,8,9]. These findings indicate a need to identify additional predictive biomarkers to select patients for immunotherapy. 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)
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