Circulating Tumor DNA Dynamics Predict Benefit from Consolidation Immunotherapy in Locally Advanced Non-Small Cell Lung Cancer

Everett J. Moding; Yufei Liu; Barzin Y. Nabet; Jacob J. Chabon; Aadel A. Chaudhuri; Angela B. Hui; Rene F. Bonilla; Ryan B. Ko; Christopher H. Yoo; Linda Gojenola; Carol D. Jones; Jianzhong He; Yawei Qiao; Ting Xu; John V. Heymach; Anne Tsao; Zhongxing Liao; Daniel R. Gomez; Millie Das; Sukhmani K. Padda; Kavitha J. Ramchandran; Joel W. Neal; Heather A. Wakelee; Billy W. Loo; Steven H. Lin; Ash A. Alizadeh; Maximilian Diehn

doi:10.1038/s43018-019-0011-0

Circulating Tumor DNA Dynamics Predict Benefit from Consolidation Immunotherapy in Locally Advanced Non-Small Cell Lung Cancer

Everett J. Moding, Yufei Liu, Barzin Y. Nabet, Jacob J. Chabon, Aadel A. Chaudhuri, Angela B. Hui, Rene F. Bonilla, Ryan B. Ko, Christopher H. Yoo, Linda Gojenola, Carol D. Jones, Jianzhong He, Yawei Qiao, Ting Xu, John V. Heymach, Anne Tsao, Zhongxing Liao, Daniel R. Gomez, Millie Das, Sukhmani K. PaddaKavitha J. Ramchandran, Joel W. Neal, Heather A. Wakelee, Billy W. Loo, Steven H. Lin, Ash A. Alizadeh, Maximilian Diehn

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Abstract

Circulating tumor DNA (ctDNA) molecular residual disease (MRD) following curative-intent treatment strongly predicts recurrence in multiple tumor types, but whether further treatment can improve outcomes in patients with MRD remains unclear. We applied CAPP-Seq ctDNA analysis to 218 samples from 65 patients receiving chemoradiation therapy (CRT) for locally advanced NSCLC, including 28 patients receiving consolidation immune checkpoint inhibition (CICI). Patients with undetectable ctDNA after CRT had excellent outcomes whether or not they received CICI. Among such patients, one died from CICI-related pneumonitis, highlighting the potential utility of only treating patients with MRD. In contrast, patients with MRD after CRT who received CICI had significantly better outcomes than patients who did not receive CICI. Furthermore, the ctDNA response pattern early during CICI identified patients responding to consolidation therapy. Our results suggest that CICI improves outcomes for NSCLC patients with MRD and that ctDNA analysis may facilitate personalization of consolidation therapy.

Original language	English (US)
Pages (from-to)	176-183
Number of pages	8
Journal	Nature Cancer
Volume	1
Issue number	2
DOIs	https://doi.org/10.1038/s43018-019-0011-0
State	Published - Feb 1 2020

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General Medicine

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Moding, E. J., Liu, Y., Nabet, B. Y., Chabon, J. J., Chaudhuri, A. A., Hui, A. B., Bonilla, R. F., Ko, R. B., Yoo, C. H., Gojenola, L., Jones, C. D., He, J., Qiao, Y., Xu, T., Heymach, J. V., Tsao, A., Liao, Z., Gomez, D. R., Das, M., ... Diehn, M. (2020). Circulating Tumor DNA Dynamics Predict Benefit from Consolidation Immunotherapy in Locally Advanced Non-Small Cell Lung Cancer. Nature Cancer, 1(2), 176-183. https://doi.org/10.1038/s43018-019-0011-0

Moding, EJ, Liu, Y, Nabet, BY, Chabon, JJ, Chaudhuri, AA, Hui, AB, Bonilla, RF, Ko, RB, Yoo, CH, Gojenola, L, Jones, CD, He, J, Qiao, Y, Xu, T , Heymach, JV , Tsao, A , Liao, Z, Gomez, DR, Das, M, Padda, SK, Ramchandran, KJ, Neal, JW, Wakelee, HA, Loo, BW, Lin, SH, Alizadeh, AA & Diehn, M 2020, 'Circulating Tumor DNA Dynamics Predict Benefit from Consolidation Immunotherapy in Locally Advanced Non-Small Cell Lung Cancer', Nature Cancer, vol. 1, no. 2, pp. 176-183. https://doi.org/10.1038/s43018-019-0011-0

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title = "Circulating Tumor DNA Dynamics Predict Benefit from Consolidation Immunotherapy in Locally Advanced Non-Small Cell Lung Cancer",

abstract = "Circulating tumor DNA (ctDNA) molecular residual disease (MRD) following curative-intent treatment strongly predicts recurrence in multiple tumor types, but whether further treatment can improve outcomes in patients with MRD remains unclear. We applied CAPP-Seq ctDNA analysis to 218 samples from 65 patients receiving chemoradiation therapy (CRT) for locally advanced NSCLC, including 28 patients receiving consolidation immune checkpoint inhibition (CICI). Patients with undetectable ctDNA after CRT had excellent outcomes whether or not they received CICI. Among such patients, one died from CICI-related pneumonitis, highlighting the potential utility of only treating patients with MRD. In contrast, patients with MRD after CRT who received CICI had significantly better outcomes than patients who did not receive CICI. Furthermore, the ctDNA response pattern early during CICI identified patients responding to consolidation therapy. Our results suggest that CICI improves outcomes for NSCLC patients with MRD and that ctDNA analysis may facilitate personalization of consolidation therapy.",

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AU - Moding, Everett J.

AU - Liu, Yufei

AU - Nabet, Barzin Y.

AU - Chabon, Jacob J.

AU - Chaudhuri, Aadel A.

AU - Hui, Angela B.

AU - Bonilla, Rene F.

AU - Ko, Ryan B.

AU - Yoo, Christopher H.

AU - Gojenola, Linda

AU - Jones, Carol D.

AU - He, Jianzhong

AU - Qiao, Yawei

AU - Xu, Ting

AU - Heymach, John V.

AU - Tsao, Anne

AU - Liao, Zhongxing

AU - Gomez, Daniel R.

AU - Das, Millie

AU - Padda, Sukhmani K.

AU - Ramchandran, Kavitha J.

AU - Neal, Joel W.

AU - Wakelee, Heather A.

AU - Loo, Billy W.

AU - Lin, Steven H.

AU - Alizadeh, Ash A.

AU - Diehn, Maximilian

PY - 2020/2/1

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N2 - Circulating tumor DNA (ctDNA) molecular residual disease (MRD) following curative-intent treatment strongly predicts recurrence in multiple tumor types, but whether further treatment can improve outcomes in patients with MRD remains unclear. We applied CAPP-Seq ctDNA analysis to 218 samples from 65 patients receiving chemoradiation therapy (CRT) for locally advanced NSCLC, including 28 patients receiving consolidation immune checkpoint inhibition (CICI). Patients with undetectable ctDNA after CRT had excellent outcomes whether or not they received CICI. Among such patients, one died from CICI-related pneumonitis, highlighting the potential utility of only treating patients with MRD. In contrast, patients with MRD after CRT who received CICI had significantly better outcomes than patients who did not receive CICI. Furthermore, the ctDNA response pattern early during CICI identified patients responding to consolidation therapy. Our results suggest that CICI improves outcomes for NSCLC patients with MRD and that ctDNA analysis may facilitate personalization of consolidation therapy.

AB - Circulating tumor DNA (ctDNA) molecular residual disease (MRD) following curative-intent treatment strongly predicts recurrence in multiple tumor types, but whether further treatment can improve outcomes in patients with MRD remains unclear. We applied CAPP-Seq ctDNA analysis to 218 samples from 65 patients receiving chemoradiation therapy (CRT) for locally advanced NSCLC, including 28 patients receiving consolidation immune checkpoint inhibition (CICI). Patients with undetectable ctDNA after CRT had excellent outcomes whether or not they received CICI. Among such patients, one died from CICI-related pneumonitis, highlighting the potential utility of only treating patients with MRD. In contrast, patients with MRD after CRT who received CICI had significantly better outcomes than patients who did not receive CICI. Furthermore, the ctDNA response pattern early during CICI identified patients responding to consolidation therapy. Our results suggest that CICI improves outcomes for NSCLC patients with MRD and that ctDNA analysis may facilitate personalization of consolidation therapy.

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Circulating Tumor DNA Dynamics Predict Benefit from Consolidation Immunotherapy in Locally Advanced Non-Small Cell Lung Cancer

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