Changes in Circulating Tumor DNA Reflect Clinical Benefit Across Multiple Studies of Patients With Non–Small-Cell Lung Cancer Treated With Immune Checkpoint Inhibitors-Reference-Cited by-同舟云学术

Changes in Circulating Tumor DNA Reflect Clinical Benefit Across Multiple Studies of Patients With Non–Small-Cell Lung Cancer Treated With Immune Checkpoint Inhibitors

Published:2022-07 Issue:6 Volume: Page:
ISSN:2473-4284
Container-title:JCO Precision Oncology
language:en
Short-container-title:JCO Precision Oncology

Author:

Vega Diana Merino¹^ORCID,Nishimura Katherine K.²^ORCID,Zariffa Névine³^ORCID,Thompson Jeffrey C.⁴^ORCID,Hoering Antje²,Cilento Vanessa²^ORCID,Rosenthal Adam²,Anagnostou Valsamo⁵^ORCID,Baden Jonathan⁶,Beaver Julia A.⁷,Chaudhuri Aadel A.⁸⁹¹⁰¹¹^ORCID,Chudova Darya¹²,Fine Alexander D.¹³^ORCID,Fiore Joseph¹⁴,Hodge Rachel¹⁵,Hodgson Darren¹⁶,Hunkapiller Nathan¹⁷¹⁸,Klass Daniel M.¹⁹,Kobie Julie²⁰,Peña Carol²¹,Pennello Gene²²^ORCID,Peterman Neil²³,Philip Reena²⁴,Quinn Katie J.¹²,Raben David²⁵,Rosner Gary L.⁵^ORCID,Sausen Mark⁶,Tezcan Ayse²³,Xia Qi²⁶,Yi Jing²⁵,Young Amanda G.¹³^ORCID,Stewart Mark D.¹^ORCID,Carpenter Erica L.²⁷^ORCID,Aggarwal Charu²⁷^ORCID,Allen Jeff¹^ORCID

Affiliation:

1. Friends of Cancer Research, Washington, DC

2. Cancer Research And Biostatistics (CRAB), Seattle, WA

3. NMD Group LLC, Bala Cynwyd, PA

4. Division of Pulmonary, Allergy and Critical Care Medicine, Thoracic Oncology Group, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA

5. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD

6. Translational Medicine, Bristol Myers Squibb, Princeton, NJ

7. Oncology Center of Excellence, Food and Drug Administration (FDA), Silver Spring, MD

8. Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO

9. Department of Genetics, Washington University School of Medicine, St Louis, MO

10. Department of Computer Science and Engineering, Washington University, St Louis, MO

11. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO

12. Guardant Health Inc, Redwood City, CA

13. Research and Development, Foundation Medicine Inc, Cambridge, MA

14. Oncology Development, Bristol Myers Squibb, Princeton, NJ

15. Late Oncology Statistics, Oncology Biometrics, AstraZeneca, Cambridge, United Kingdom

16. Translational Medicine, Oncology Research & Development, AstraZeneca, Waltham, MA

17. GRAIL, Menlo Park, CA

18. During the conduct of this work and development of the manuscript, N.H. was affiliated with GRAIL, Inc; however, is not affiliated with GRAIL, Inc at the time of submission.

19. Assay Development, Roche Sequencing Solutions, Pleasanton, CA

20. Translational Oncology, Early Oncology Statistics, Merck Research Laboratories, Kenilworth, NJ

21. Companion Diagnostics, Oncology Early Development, Merck Research Laboratories, Kenilworth, NJ

22. Division of Imaging, Diagnostics, and Software Reliability, Office of Science and Engineering Laboratories, Food and Drug Administration (FDA), Silver Spring, MD

23. Foundation Medicine Inc, San Diego, CA

24. Division of Molecular Genetics, Office of Health Technology 7 (In Vitro Diagnostics and Radiological Health), Food and Drug Administration (FDA), Silver Spring, MD

25. Product Development Oncology, Genentech Inc, South San Francisco, CA

26. Product Development Data Sciences, Genentech Inc, South San Francisco, CA

27. Division of Hematology and Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA

Abstract

PURPOSE As immune checkpoint inhibitors (ICI) become increasingly used in frontline settings, identifying early indicators of response is needed. Recent studies suggest a role for circulating tumor DNA (ctDNA) in monitoring response to ICI, but uncertainty exists in the generalizability of these studies. Here, the role of ctDNA for monitoring response to ICI is assessed through a standardized approach by assessing clinical trial data from five independent studies. PATIENTS AND METHODS Patient-level clinical and ctDNA data were pooled and harmonized from 200 patients across five independent clinical trials investigating the treatment of patients with non–small-cell lung cancer with programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1)–directed monotherapy or in combination with chemotherapy. CtDNA levels were measured using different ctDNA assays across the studies. Maximum variant allele frequencies were calculated using all somatic tumor-derived variants in each unique patient sample to correlate ctDNA changes with overall survival (OS) and progression-free survival (PFS). RESULTS We observed strong associations between reductions in ctDNA levels from on-treatment liquid biopsies with improved OS (OS; hazard ratio, 2.28; 95% CI, 1.62 to 3.20; P < .001) and PFS (PFS; hazard ratio 1.76; 95% CI, 1.31 to 2.36; P < .001). Changes in the maximum variant allele frequencies ctDNA values showed strong association across different outcomes. CONCLUSION In this pooled analysis of five independent clinical trials, consistent and robust associations between reductions in ctDNA and outcomes were found across multiple end points assessed in patients with non–small-cell lung cancer treated with an ICI. Additional tumor types, stages, and drug classes should be included in future analyses to further validate this. CtDNA may serve as an important tool in clinical development and an early indicator of treatment benefit.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

Link

https://ascopubs.org/doi/pdfdirect/10.1200/PO.21.00372

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