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Poster display session

3183 - Assessing response to immunotherapy in patients with non-small cell lung cancer using circulating tumor DNA

Date

09 Sep 2017

Session

Poster display session

Presenters

Sarah Goldberg

Citation

Annals of Oncology (2017) 28 (suppl_5): v460-v496. 10.1093/annonc/mdx380

Authors

S.B. Goldberg1, A. Narayan2, A.J. Kole2, R.H. Decker2, J. Teysir2, N.J. Carriero3, A. Lee2, R. Nemati2, S.K. Nath2, S.M. Mane4, Y. Deng5, N. Sukumar5, D. Zelterman5, D.J. Boffa6, K. Politi7, S.N. Gettinger1, L.D. Wilson2, R.S. Herbst1, A.A. Patel2

Author affiliations

  • 1 Medicine (medical Oncology), Yale University School of Medicine, 06520-8032 - New Haven/US
  • 2 Therapeutic Radiology, Yale University School of Medicine, 06520-8032 - New Haven/US
  • 3 Scientific Computing Core, Simon's Foundation, New York/US
  • 4 Genetics, Yale University School of Medicine, 06520-8032 - New Haven/US
  • 5 Biostatistics, Yale University School of Medicine, 06520-8032 - New Haven/US
  • 6 Thoracic Surgery, Yale University School of Medicine, 06520-8032 - New Haven/US
  • 7 Pathology, Yale University School of Medicine, 06520-8032 - New Haven/US
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Resources

Abstract 3183

Background

Evaluation of response to immune checkpoint inhibitors by serial imaging can be complicated by the possibility of pseudo-progression or delayed response, sometimes resulting in discontinuation of an effective therapy or delay of alternate treatment. Monitoring tumor cell death by measuring changes in circulating tumor DNA (ctDNA) levels in blood may permit early assessment of immunotherapy efficacy.

Methods

We examined ctDNA levels in plasma samples from patients with metastatic non-small cell lung cancer (NSCLC) undergoing treatment with a PD-1 or PD-L1 inhibitor. CtDNA was quantified in plasma by determining the allele fraction of cancer-associated somatic mutations using a multi-gene next-generation sequencing assay. A ctDNA response was defined as more than 50% decrease in mutant allele fraction from baseline, with a second confirmatory measurement. Radiographic response assessment was performed using RECIST 1.1. Changes in ctDNA levels over time were correlated with imaging findings and with clinical outcomes.

Results

Twenty-eight patients with metastatic NSCLC had ctDNA quantified in serial blood samples collected before and during treatment with a PD-1 axis inhibitor. Strong agreement was observed between ctDNA response and radiographic response (Cohen’s Kappa = 0.753, P 

Conclusions

An early drop in ctDNA level enables assessment of response to immune checkpoint inhibitor therapies at a time when radiographic response may be uncertain for patients with metastatic NSCLC. Achievement of such a ctDNA response is predictive of a longer duration of therapeutic benefit as well as superior PFS and OS.

Clinical trial identification

Legal entity responsible for the study

Yale University

Funding

The National Cancer Institute (RO1-CA197486-01A1), the Yale SPORE in Lung Cancer (P50-CA196530), the LUNGevity Foundation, the Honorable Tina Brozman Foundation, the Kalimeris Fund, and the Yale Cancer Center.

Disclosure

S.B. Goldberg: Research funding from AstraZeneca. Membership on an AstraZeneca advisory board. A.J. Kole: Immediate family member is employed by and owns stock in Sarepta Therapeutics. R.H. Decker: Research support from Merck. Advisory board for Regeneron. K. Politi: Research support from Astra Zeneca, Roche, and Kolltan. Consultant for AstraZeneca, Novartis, and Merck. MSKCC for IP licensed to Molecular MD. S.N. Gettinger: Consultant for Bristol Myers Squibb and Alexion. L.D. Wilson: Owns stock in Medtronic, Alexion, Biogen, Bristol Myers Squibb, Celgene, Johnson and Johnson, Merck, United Health, and Vertex. R.S. Herbst: Research support from Genetech and Merck. Advisory board for AstraZeneca, Eli Lilly, Genentech/Roche, Merck and Pfizer. A.A. Patel: Research support from AstraZeneca. Advisory board for Novartis. Patent application covering circulating tumor DNA assay. All other authors have declared no conflicts of interest.

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