588P - PLCRC-PROVENC3 study: Prognostic value of post-surgery liquid biopsy circulating tumor DNA in stage III colon cancer patients

Background

Surgery followed by adjuvant chemotherapy (ACT) is standard of care in stage III colon cancer. However, only 15-20% of the patients truly benefit from ACT because 55% was cured by surgery alone and 25-30% develop recurrences despite ACT. Post-surgery circulating tumor DNA (ctDNA) is a biomarker for minimal residual disease, which may facilitate stratification of stage III colon cancer patients for ACT treatment decisions. The aim of this study is to determine the prognostic value and clinical validity of post-surgery ctDNA-testing in stage III colon cancer patients.

Methods

236 stage III colon cancer patients treated with ACT were included in the PROVENC3 study. Blood was collected pre-surgery, post-surgery and post-ACT. Tumor-informed detection of plasma ctDNA was performed through integrated whole genome sequencing (WGS) analyses of formalin-fixed paraffin-embedded tumor tissue DNA (80x), germline DNA (40x), and plasma cell-free DNA (30x). Outcome measurement is time to recurrence (TTR).

Results

From 124 patients (median follow up: 31 months) show a worse TTR of ctDNA-positive patients [HR: 4.7, 95%CI: (2,37-9,3), p<0.001]. 64% of the ctDNA positive, and 21% of the ctDNA negative patients experienced a recurrence. 40% of the patients who experienced a recurrence were ctDNA positive post-surgery. TTR was significantly different per ctDNA status, with a shorter median TTR for ctDNA-positive compared to ctDNA-negative patients (7.7 vs 13.1 months). Final results from the complete cohort with median follow up of 41 months will be presented in October 2023.

Conclusions

Post-surgery ctDNA detection by WGS is a strong prognostic biomarker in stage III colon cancer patients. Importantly, part of the ctDNA-positive patients did not experience a recurrence and were likely cured by ACT. Approximately 60% of the recurrences were not detected by post-surgery ctDNA-testing. Ultimately, the results of this study will be used to model and design a ctDNA-guided interventional trial in stage III colon cancer patients, to reduce futile ACT and its associated negative side-effects.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Prospective Dutch Colorectal Cancer Cohort (PLCRC).

Funding

Dutch Cancer Society (KWF #11809), Health Holland (#LSHM19027), The Mark Foundation for Cancer Research, Personal Genome Diagnostics.

Disclosure

C. Rubio-Alarcón: Non-Financial Interests, Non financial benefits: Personal genome diagnostics, Cergentis BV. V. Velculescu: Financial Interests, , Member of Board of Directors, board member, consultant and stock shareholder: Personal genome diagnostics, Delfi diagnostics. S. Angiuoli, A. Georgiadis, D. Riley, C. Greco: Financial Interests, Member: Personal Genome Diagnostics. D. Van Den Broek: Financial Interests, Expert Testimony, has provided lectures, expert testimony, and advisory board presence, for Roche diagnostics, all outside the submitted work and all financial supports transferred to institute: Roche diagnostics. C.J.A. Punt: Financial Interests, Institutional, Advisory Board: Nordic Group BV. M. Koopman: Financial Interests, Institutional, Advisory Board, advisory board and speaker: Pierre Fabre; Financial Interests, Institutional, Advisory Board: MSD, Bayer; Financial Interests, Institutional, Advisory Board, Advisory Board, speaker: Servier; Financial Interests, Institutional, Invited Speaker: Merck, Bristol Myers Squibb; Financial Interests, Institutional, Trial Chair: Servier; Financial Interests, Institutional, Research Grant: Servier, Roche, Bayer, Bristol Myers Squibb, Merck, Personal Genomics Diagnostics, Sirtex, Pierre Fabre; Financial Interests, Institutional, Funding: Pierre Fabre, Amgen, Nordic Pharma, Novartis, Merck, Servier, Bristol Myers Squibb; Non-Financial Interests, Leadership Role, vice-chair of DCCG: Dutch Colorectal Cancer Group; Non-Financial Interests, Advisory Role, Member of KWF scientific board: KWF; Non-Financial Interests, Other, ESMO faculty member for the Gastro-Intestinal Tumours – colorectal cancer: ESMO; Non-Financial Interests, Advisory Role, expert member of committee “regie op registers dure geneesmiddelen” ZINNL: ZiNNL; Non-Financial Interests, Advisory Role, CRC expert on Kanker.nl platform for answering online CRC questions of CRC (non) patients: Patient respresentative organisation (Kanker.nl); Non-Financial Interests, Leadership Role, chair of RWD & DH working group: ESMO; Other, PI of the Dutch Prospective Colorectal Cancer Cohort study: PLCRC project. J.M.L. Roodhart: Financial Interests, Research Funding: Bayer, Bristol Myers Squibb, Merck-Serono, Pierre Fabre, Servier, HUB 4 organoids, Cleara Biotech. G. Meijer: Financial Interests, Member of Board of Directors, co-founder and board member (CSO): CRCbioscreen BV; Financial Interests, Research Funding: CZ Health Insurances; Financial Interests, Research Funding, these companies provide materials, equipment and/or sample/genomic analyses: Exact Sciences, Sysmex, Sentinel Ch. SpA, Personal Genome Diagnostics, DELFi, Hartwig Medical Foundation. M. Sausen: Financial Interests, Member: Personal Genome Diagnostics. G.R. Vink: Financial Interests, Research Funding: Bristol Myers Squibb, Merck, Servier, Personal Genome Diagnostics, Bayer, Sirtex, Pierre Fabre, Lilly, Delfi Diagnostics. R. Fijneman: Financial Interests, Research Funding, public private partnership consortia grants: Cergentis BV Personal Genome Diagnostics, Delfi Diagnostics, Merck BV. All other authors have declared no conflicts of interest.