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 Jr; 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

Nat Cancer. 2020 Feb;1(2):176-183. doi: 10.1038/s43018-019-0011-0. Epub 2020 Jan 20.

Authors

Everett J Moding^{1

2}, Yufei Liu³, Barzin Y Nabet², Jacob J Chabon², Aadel A Chaudhuri⁴, Angela B Hui², Rene F Bonilla¹, Ryan B Ko¹, Christopher H Yoo¹, Linda Gojenola⁵, Carol D Jones⁵, Jianzhong He³, Yawei Qiao³, Ting Xu³, John V Heymach⁶, Anne Tsao⁶, Zhongxing Liao³, Daniel R Gomez^{3

7}, Millie Das^{8

9}, Sukhmani K Padda⁸, Kavitha J Ramchandran⁸, Joel W Neal⁸, Heather A Wakelee⁸, Billy W Loo Jr¹, Steven H Lin^#¹⁰, Ash A Alizadeh^#^{11

12

13}, Maximilian Diehn^#^{14

15

16}

Affiliations

¹ Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
² Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
³ Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁴ Department of Radiation Oncology, Washington University, St. Louis, MO, USA.
⁵ Department of Pathology, Stanford University, Stanford, CA, USA.
⁶ Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁷ Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁸ Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
⁹ Department of Medicine, VA Palo Alto Health Care System, Palo Alto, CA, USA.
¹⁰ Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. SHLin@mdanderson.org.
¹¹ Stanford Cancer Institute, Stanford University, Stanford, CA, USA. arasha@stanford.edu.
¹² Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA. arasha@stanford.edu.
¹³ Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA. arasha@stanford.edu.
¹⁴ Department of Radiation Oncology, Stanford University, Stanford, CA, USA. diehn@stanford.edu.
¹⁵ Stanford Cancer Institute, Stanford University, Stanford, CA, USA. diehn@stanford.edu.
¹⁶ Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA. diehn@stanford.edu.

^# Contributed equally.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Non-Small-Cell Lung* / genetics
Circulating Tumor DNA* / genetics
Disease Progression
Humans
Immunotherapy
Lung Neoplasms* / therapy
Neoplasm, Residual / genetics

Substances

Circulating Tumor DNA

Abstract

Publication types

MeSH terms

Substances

Grants and funding