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Poster Display session 3

4689 - Analysis of Circulating Tumor DNA for Early Relapse Detection in Stage III Colorectal Cancer After Adjuvant Chemotherapy

Date

30 Sep 2019

Session

Poster Display session 3

Topics

Translational Research

Tumour Site

Presenters

Samuel Jacobs

Citation

Annals of Oncology (2019) 30 (suppl_5): v25-v54. 10.1093/annonc/mdz239

Authors

S.A. Jacobs1, H. Sethi2, T. Kolveska3, T.J. George4, S. Shchegrova2, A.S. Tin2, J. Lee5, A. Olson2, D. Renner2, E. Kalashnikova6, G. Yothers7, N. Wolmark8, K. Pogue-Geile9, A. Srinivasan1, J. Kortmansky10, M. Louie6, R. Salari2, B. Zimmermann2, A. Aleshin6, C.J. Allegra1

Author affiliations

  • 1 Oncology, National Surgical Adjuvant Breast and Bowel Project, 15212 - Pittsburgh/US
  • 2 R&d, Natera, Inc., 94070 - San Carlos/US
  • 3 Oncology Clinical Trials Program, Kaiser Permanente, 94589 - Vallejo/US
  • 4 Gi Oncology Program, University of Florida, 32610 - Gainesville/US
  • 5 Department Of Medicine, University of Pittsburgh, 15261 - Pittsburgh/US
  • 6 Oncology, Natera, Inc., 94070 - San Carlos/US
  • 7 Nrg Oncology, University of Pittsburgh, 15261 - Pittsburgh/US
  • 8 Allegheny Cancer Center, Allegheny Health Network Cancer Institute, 15212 - Pittsburgh/US
  • 9 Molecular Pathology Laboratory, National Surgical Adjuvant Breast and Bowel Project, 15212 - Pittsburgh/US
  • 10 Clinical Medicine: Medical Oncology, Yale Cancer Center, 06520 - New Haven/US

Resources

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Abstract 4689

Background

Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for early prediction of relapse across different tumor types. In patients with colorectal cancer (CRC), multiple studies have analyzed ctDNA to monitor tumor burden using fixed gene panels and droplet digital PCR. Here, we use a highly sensitive and specific, bespoke, whole exome-based NGS approach (Signatera™) for ctDNA monitoring.

Methods

A cohort of 33 patients with stage III CRC who underwent surgery and were treated with at least 4 months of adjuvant chemotherapy was analyzed. Mutational profiles derived from primary tumor tissue and germline DNA whole exome were used to design assays targeting tumor-specific somatic variants. The bespoke assays were used for ctDNA detection in plasma samples. Relapse-free survival (RFS) was calculated for patients stratified by ctDNA status.

Results

Plasma samples (n = 44; average volume=1.8mL) from patients (N = 33) were analysed for the presence of ctDNA. Of the five ctDNA-positive patients, clinical follow-up was available for three patients, all of whom relapsed (100%; 3/3); three of 27 ctDNA-negative patients (11%) also clinically relapsed. Molecular relapse through ctDNA analysis was detected up to 668 days ahead of radiological imaging with an average lead time of 305 days. The majority of relapses in ctDNA-positive patients (67%; 2/3) occurred within a year of follow-up, while no relapses were observed in ctDNA-negative patients during the one-year time frame. All plasma samples (n = 34) from 24 non-relapsing patients were ctDNA negative, corresponding to a specificity of 100%. The presence of ctDNA was associated with a markedly reduced RFS compared to ctDNA-negative patients (HR: 5.6; 95% CI: 0.6-52.1; p < 0.01).

Conclusions

The study results indicate that ctDNA status is associated with high relapse risk in patients with CRC and can serve as a predictor of patient outcome. Despite low plasma volumes (<5mL) and lack of longitudinal samples for analysis, ctDNA was detected in 50% of relapse cases.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Natera, Inc. and NSABP Foundation.

Funding

Natera, Inc., Bayer, NSABP Foundation.

Disclosure

H. Sethi: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. T.J. George: Research grant / Funding (institution): Merck; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Pharmacyclics. S. Shchegrova: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. A.S. Tin: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. A. Olson: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. D. Renner: Full / Part-time employment: Natera, Inc. E. Kalashnikova: Full / Part-time employment: Natera, Inc. M. Louie: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. R. Salari: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. B. Zimmermann: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. A. Aleshin: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. All other authors have declared no conflicts of interest.

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