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

doi:10.18632/ONCOTARGET.28178

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

Producción científica: Article › revisión exhaustiva

6 Citas (Scopus)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	257-270
Número de páginas	14
Publicación	Oncotarget
Volumen	13
DOI	https://doi.org/10.18632/ONCOTARGET.28178
Estado	Published - ene 31 2022

Nota bibliográfica

Publisher Copyright:
© 2022 Willis et al.

Financiación

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

Financiadores	Número del financiador
National Institutes of Health (NIH)	TL1R002493
Bristol-Myers Squibb
AstraZeneca
National Center for Advancing Translational Sciences (NCATS)	UL1TR002494, UL1TR002538
University of Utah

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

Good health and well being

ASJC Scopus subject areas

Oncology

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10.18632/ONCOTARGET.28178

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Willis, C., Bauer, H., Au, T. H., Menon, J., Unni, S., Tran, D., Rivers, Z., Akerley, W., Schabath, M. B., Badin, F., Sekhon, A., Patel, M., Xia, B., Gustafson, B., Villano, J. L., Thomas, J. M., Lubinga, S. J., Cantrell, M. A., Brixner, D., & Stenehjem, D. (2022). Real-world survival analysis by tumor mutational burden in non-small cell lung cancer: A multisite U.S. study. Oncotarget, 13, 257-270. https://doi.org/10.18632/ONCOTARGET.28178

@article{b38658bdf6554a9187e9fefe2db56450,

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

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.",

keywords = "Immunotherapy, Lung neoplasma, Tumor biomarkers",

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

note = "Publisher Copyright: {\textcopyright} 2022 Willis et al.",

year = "2022",

month = jan,

day = "31",

doi = "10.18632/ONCOTARGET.28178",

language = "English",

volume = "13",

pages = "257--270",

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Willis, C, Bauer, H, Au, TH, Menon, J, Unni, S, Tran, D, Rivers, Z, Akerley, W, Schabath, MB, Badin, F, Sekhon, A, Patel, M, Xia, B, Gustafson, B, Villano, JL, Thomas, JM, Lubinga, SJ, Cantrell, MA, Brixner, D & Stenehjem, D 2022, 'Real-world survival analysis by tumor mutational burden in non-small cell lung cancer: A multisite U.S. study', Oncotarget, vol. 13, pp. 257-270. https://doi.org/10.18632/ONCOTARGET.28178

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

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

UR - https://www.scopus.com/pages/publications/85124670586

UR - https://www.scopus.com/pages/publications/85124670586#tab=citedBy

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 -

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

Resumen

Nota bibliográfica

Financiación

ODS de las Naciones Unidas

ASJC Scopus subject areas

Acceder al documento

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Huella

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