Abstract 1649P
Background
Signatera™ is a personalized commercial assay that detects circulating tumor DNA (ctDNA) and has shown molecular residual disease (MRD) in colorectal and urothelial cancer. However, it is unknown whether Signatera™ could detect ctDNA in anaplastic (ATC) and medullary thyroid cancer (MTC) due to their low mutation burden.
Methods
Single-center study of ATC and MTC patients (pts) who underwent ctDNA testing from 1/2021-4/2022 using Signatera™. Tumor tissue was obtained from each pt (per std. of care), and blood samples were collected at restaging visits. Tumor tissue and matched normal were whole exome sequenced (WES) to obtain up to 16 clonal somatic variants to be tracked in plasma. Sample is ctDNA positive when at least 2/16 variants are detected in plasma. ctDNA results were correlated with imaging and tumor markers (TM).
Results
Nine pts (5 MTC, 4 ATC) were included and ctDNA assays were developed for all. A 16-variant assay was built for 7/9 (78%) pts (4 MTC, 3ATC). The remaining 2 pts had 6 (MTC) and 2 (ATC) somatic variants. Both were negative for ctDNA; 1 was false negative due to evidence of disease. Of the 4 MTC pts with the 16-variant assay, 2 showed ctDNA that correlated with disease status and TM. The first pt had growing lesions that correlated with increase in calcitonin (Ctn), CEA, and ctDNA. The 2nd pt had decrease in Ctn, CEA, and ctDNA after partial response to selpercatinib. Two of 3 ATC pts with the 16-variant assay had enough follow-up. Pt 1 had a false negative ctDNA. Pt 2 was NRAS, stage IVB with undetectable ctDNA after surgical resection and adjuvant chemoRT, followed by its reappearance. There was persistent no evidence of disease despite rising ctDNA, suggesting MRD. Pembrolizumab was started and ctDNA became negative.
Conclusions
This is the first reported study to show detectable ctDNA using Signatera™ in MTC and ATC. We observed that tumor biology with lower prevalence of somatic variants could lead to insufficient number of designable clonal variants from WES, which could impact the sensitivity of the assay. Additionally, in 3/6 evaluable pts, ctDNA correlated with progression or treatment response. Further research is needed to study the role of Signatera™ in thyroid cancer, especially in ATC and MTC where TM are often not useful or can be difficult to interpret.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Natera.
Funding
Natera.
Disclosure
M.E. Cabanillas: Non-Financial Interests, Personal, Advisory Board: Exelixis; Non-Financial Interests, Personal, Advisory Role: Lilly , Bayer; Non-Financial Interests, Personal, Principal Investigator: Genentech, Merck. M.I. Hu: Non-Financial Interests, Personal, Advisory Board, Research Support: Eli Lilly. N.L. Busaidy: Non-Financial Interests, Personal, Advisory Role: Exelixis, Eisai. R. Dadu: Non-Financial Interests, Personal, Research Grant: Eisai, Merck, Exlixis, Astazeneca; Non-Financial Interests, Personal, Advisory Board: Exelixis. G. Budde: Financial Interests, Personal and Institutional, Full or part-time Employment: Natera. M. Malhotra: Financial Interests, Personal and Institutional, Full or part-time Employment: Natera. M.E. Zafereo: Non-Financial Interests, Personal, Principal Investigator: Eli Lilly, Merck. All other authors have declared no conflicts of interest.