TY - JOUR
T1 - Real-world survival analysis by tumor mutational burden in non-small cell lung cancer
T2 - A multisite U.S. study
AU - Willis, Connor
AU - Bauer, Hillevi
AU - Au, Trang H.
AU - Menon, Jyothi
AU - Unni, Sudhir
AU - Tran, Dao
AU - Rivers, Zachary
AU - Akerley, Wallace
AU - Schabath, Matthew B.
AU - Badin, Firas
AU - Sekhon, Ashley
AU - Patel, Malini
AU - Xia, Bing
AU - Gustafson, Beth
AU - Villano, John L.
AU - Thomas, John Michael
AU - Lubinga, Solomon J.
AU - Cantrell, Michael A.
AU - Brixner, Diana
AU - Stenehjem, David
N1 - Publisher Copyright:
© 2022 Willis et al.
PY - 2022/1/31
Y1 - 2022/1/31
N2 - 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.
AB - 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.
KW - Immunotherapy
KW - Lung neoplasma
KW - Tumor biomarkers
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U2 - 10.18632/ONCOTARGET.28178
DO - 10.18632/ONCOTARGET.28178
M3 - Article
C2 - 35111281
AN - SCOPUS:85124670586
SN - 1949-2553
VL - 13
SP - 257
EP - 270
JO - Oncotarget
JF - Oncotarget
ER -
