Abstract 91P
Background
Liquid biopsy can detect small fragments of cell-free DNA (cfDNA) shed into the circulation from tumor tissue. These fragments, also called circulating tumor DNA (ctDNA), can be used to detect minimal residual disease in patients with metastatic colorectal cancer who have no evidence of disease after resection of metastases.
Methods
We enrolled patients with metastatic colorectal cancer to the liver who underwent complete liver metastasectomy after neoadjuvant therapy. Peripheral blood samples were collected at different timepoints before (median 11 days) and after (median 93 days) surgery. DNA was isolated from an average of 2 ml plasma and was tested for molecular alterations identified in the tumor tissue of KRAS, TP53, SMAD4, BRAF, PIK3CA, NRAS, MTOR, APEX1, PTEN, ERBB4, KDR, FBXW7, and SPOP genes. We used a novel ultrasensitive droplet digital PCR (BioRad) to detect mutated ctDNA in pre-amplified cfDNA with a sensitivity up to 2 mutant copies in the wild-type background. The median number of tested mutations in each patient was 2.
Results
We collected 77 plasma cfDNA samples from 24 patients (median age at diagnosis, 51) with stage IV colorectal cancer. Of these 24 patients, 15 (62.5%) developed disease recurrence after metastatectomy with a median disease-free survival of 77 weeks. ctDNA was detected in 6 (42.9%) of 14 patients with available cfDNA samples collected before surgery and in 4 (16.7%) of 24 patients with available cfDNA samples collected after surgery. When analyzing all 77 cfDNA samples, presurgical cfDNA samples showed more frequently ctDNA detection compared to postsurgical samples (34.4% [11/32] vs 13.3% [6/45], p=0.028). However, neither ctDNA detection before or after surgery was associated with significant difference in relapse-free survival (all p>0.6), which could have been due to limited plasma volume, small sample size and heterogeneity in timing of blood collection.
Conclusions
An ultrasensitive ddPCR detects ctDNA in pre- and postsurgical plasma samples from proportion of patients with colorectal cancer with isolated liver metastases, who are candidates for radical metastasectomy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The University of Texas MD Anderson Cancer Center.
Funding
Rising Tide Foundation.
Disclosure
M.J. Overman: Financial Interests, Advisory Role, Consulting: Merck Sharp & Dohme Corp; Financial Interests, Advisory Role, Consulting: AbbVie; Financial Interests, Advisory Role, Consulting: Agilvax; Financial Interests, Advisory Role, Consulting: Acrotech Biopharma; Financial Interests, Advisory Board: Takeda Pharmaceuticals (Japan). N..A. Dasari: Financial Interests, Sponsor/Funding, Research Funding: Guardant Health. F. Meric-Bernstam: Financial Interests, Advisory Role, Consulting: AbbVie; Financial Interests, Advisory Role, Consulting: Aduro BioTech Inc.; Financial Interests, Advisory Role, Consulting: Alkermes; Financial Interests, Advisory Role, Consulting: AstraZeneca; Financial Interests, Advisory Role, Consulting: DebioPharm; Financial Interests, Advisory Role, Consulting: eFFECTOR Therapeutics; Financial Interests, Advisory Role, Consulting: F. Hoffman-La Roche Ltd.; Financial Interests, Advisory Role, Consulting: Genentech Inc.; Financial Interests, Advisory Role, Consulting: IBM Watson; Financial Interests, Advisory Role, Consulting: Infinity Pharmaceuticals; Financial Interests, Advisory Role, Consulting: Jackson Laboratory; Financial Interests, Advisory Role, Consulting: Kolon Life Science; Financial Interests, Advisory Role, Consulting: OrigiMed; Financial Interests, Advisory Role, Consulting: PACT Pharma; Financial Interests, Advisory Role, Consulting: Parexel International; Financial Interests, Advisory Role, Consulting: Pfizer Inc.; Financial Interests, Advisory Role, Consulting: Samsung Bioepis; Financial Interests, Advisory Role, Consulting: Seattle Genetics Inc.; Financial Interests, Advisory Role, Consulting: Tyra Biosciences; Financial Interests, Advisory Role, Consulting: Xencor; Financial Interests, Advisory Role, Consulting: Zymeworks; Financial Interests, Advisory Board: Immunomedics; Financial Interests, Advisory Board: Inflection Biosciences; Financial Interests, Advisory Board: Mersana Therapeutics; Financial Interests, Advisory Board: Puma Biotechnology Inc; Financial Interests, Advisory Board: Seattle Genetics; Financial Interests, Advisory Board: Silverback Therapeutics; Financial Interests, Advisory Board: Spectrum Pharmaceuticals; Financial Interests, Advisory Board: Zentalis; Financial Interests, Other, Honoraria: Chugai Biopharmaceuticals; Financial Interests, Other, Honoraria: Mayo Clinic; Financial Interests, Other, Honoraria: Rutgers Cancer Institute of New Jersey; Financial Interests, Sponsor/Funding, Sponsored Research: Aileron Therapeutics; Financial Interests, Sponsor/Funding, Sponsored Research: AstraZeneca; Financial Interests, Sponsor/Funding, Sponsored Research: Bayer Healthcare Pharmaceutical; Financial Interests, Sponsor/Funding, Sponsored Research: Calithera Biosciences Inc; Financial Interests, Sponsor/Funding, Sponsored Research: Curis Inc; Financial Interests, Sponsor/Funding, Sponsored Research: CytomX Therapeutics Inc; Financial Interests, Sponsor/Funding, Sponsored Research: Daiichi Sankyo Co. Ltd; Financial Interests, Sponsor/Funding, Sponsored Research: Debiopharm International; Financial Interests, Sponsor/Funding, Sponsored Research: eFFECTOR Therapeutics; Financial Interests, Sponsor/Funding, Sponsored Research: Genentech; Financial Interests, Sponsor/Funding, Sponsored Research: Guardant Health; Financial Interests, Sponsor/Funding, Sponsored Research: Klus Pharma; Financial Interests, Sponsor/Funding, Sponsored Research: Takeda Pharmaceutical (formerly Millennium Pharmaceutical); Financial Interests, Sponsor/Funding, Sponsored Research: Novartis; Financial Interests, Sponsor/Funding, Sponsored Research: Puma Biotechnology; Financial Interests, Sponsor/Funding, Sponsored Research: Taiho Pharmaceutical Co.; Financial Interests, Other, Travel-Related: Beth Israel Deaconess Medical Center. S. Kopetz: Financial Interests, Advisory Role, Consulting: Roche; Financial Interests, Advisory Role, Consulting: Genentech; Financial Interests, Advisory Role, Consulting: EMD Serono; Financial Interests, Advisory Role, Consulting: Merck; Financial Interests, Advisory Role, Consulting: Karyopharm Therapeutics; Financial Interests, Advisory Role, Consulting: Amal Therapeutics; Financial Interests, Advisory Role, Consulting: Navire Pharma; Financial Interests, Advisory Role, Consulting: Symphogen; Financial Interests, Advisory Role, Consulting: Holy Stone; Financial Interests, Advisory Role, Consulting: Biocartis; Financial Interests, Advisory Role, Consulting: Amgen; Financial Interests, Advisory Role, Consulting: Novartis; Financial Interests, Advisory Role, Consulting: Lilly; Financial Interests, Advisory Role, Consulting: Boehringer Ingelheim; Financial Interests, Advisory Role, Consulting: Boston Biomedical; Financial Interests, Advisory Role, Consulting: AstraZeneca/MedImmune; Financial Interests, Advisory Role, Consulting: Bayer Health; Financial Interests, Advisory Role, Consulting: Pierre Fabre; Financial Interests, Advisory Role, Consulting: Redx Pharma. F. Janku: Financial Interests, Institutional, Research Grant, Research Funding: Agios; Financial Interests, Institutional, Research Grant, Research Funding: Asana; Financial Interests, Institutional, Research Grant, Research Funding: Astellas; Financial Interests, Institutional, Research Grant, Research Funding: Astex; Financial Interests, Institutional, Research Grant, Research Funding: Bayer; Financial Interests, Institutional, Research Grant, Research Funding: Bicara; Financial Interests, Institutional, Research Grant, Research Funding: BioMed Valley Discoveries; Financial Interests, Institutional, Research Grant, Research Funding: Bioxcel; Financial Interests, Institutional, Research Grant, Research Funding: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant, Research Funding: Deciphera; Financial Interests, Institutional, Research Grant, Research Funding: FujiFilm Pharma; Financial Interests, Institutional, Research Grant, Research Funding: Genentech; Financial Interests, Institutional, Research Grant, Research Funding: Ideaya; Financial Interests, Institutional, Research Grant, Research Funding: JS Innopharm; Financial Interests, Institutional, Research Grant, Research Funding: Lilly; Financial Interests, Institutional, Research Grant, Research Funding: Merck; Financial Interests, Institutional, Research Grant, Research Funding: Novartis; Financial Interests, Institutional, Research Grant, Research Funding: Novellus; Financial Interests, Institutional, Research Grant, Research Funding: Plexxikon; Financial Interests, Institutional, Research Grant, Research Funding: Proximagen; Financial Interests, Institutional, Research Grant, Research Funding: Sanofi; Financial Interests, Institutional, Research Grant, Research Funding: Sotio; Financial Interests, Institutional, Research Grant, Research Funding: SpringBank Pharmaceuticals; Financial Interests, Institutional, Research Grant, Research Funding: SQZ Biotechnologies; Financial Interests, Institutional, Research Grant, Research Funding: Synlogic; Financial Interests, Institutional, Research Grant, Research Funding: Synthorx; Financial Interests, Institutional, Research Grant, Research Funding: Symphogen; Financial Interests, Advisory Role, Consulting: Asana; Financial Interests, Advisory Role, Consulting: Baush Health; Financial Interests, Advisory Role, Consulting: Cardiff Oncology; Financial Interests, Advisory Role, Consulting: Deciphera; Financial Interests, Advisory Role, Consulting: Guardant Health; Financial Interests, Advisory Role, Consulting: Ideaya; Financial Interests, Advisory Role, Consulting: IFM Therapeutics; Financial Interests, Advisory Role, Consulting: Immunomet; Financial Interests, Advisory Role, Consulting: Illumina; Financial Interests, Advisory Role, Consulting: Jazz Pharmaceuticals; Financial Interests, Advisory Role, Consulting: Novartis; Financial Interests, Advisory Role, Consulting: PureTech Health; Financial Interests, Advisory Role, Consulting: Sotio; Financial Interests, Advisory Role, Consulting: Synlogic; Financial Interests, Ownership Interest: Cardiff Oncology; Financial Interests, Other: Bio-Rad; Financial Interests, Other: Biocartis. All other authors have declared no conflicts of interest.