164P - Early evaluation of effectiveness and cost-effectiveness of ctDNA-guided selection for adjuvant chemotherapy in stage II colon cancer

Background

After curative surgery for stage II colon cancer (CC-II), only patients with high-risk features (pT4 tumor and MSS status) are offered adjuvant chemotherapy (ACT) in the Netherlands. Nevertheless, 15% of CC-II patients develop a recurrence. Post-operative circulating tumor DNA (ctDNA) is a prognostic biomarker that could improve selection of patients that may benefit from ACT. We performed an early evaluation of the effectiveness and cost-effectiveness of ctDNA-guided selection for ACT in CC-II in the Netherlands.

Methods

The validated PATTERN model, which simulates the course of disease from diagnosis till death in CC-II, was supplemented with data on the prognostic value of ctDNA from the Dutch PLCRC-MEDOCC study. Five strategies for selecting patients for ACT were evaluated: current guideline strategy (pT4 and MSS), ctDNA-only strategy, and three combination strategies of ctDNA in addition to pT4 and MSS status. For each strategy, we estimated costs, (quality-adjusted) life-years (QALYs), recurrences and CC deaths. The impact of uncertainty concerning strategy adherence, treatment effect of ACT, costs of ctDNA testing, and test performance on cost-effectiveness was assessed in sensitivity analyses.

Results

Model predictions showed that the ctDNA-only strategy was less effective (more recurrences, less QALYs) and that the combination strategies were more effective (less recurrences, more QALYs) than the current guideline strategy. From the viewpoint of cost-effectiveness, using a willingness-to-pay threshold of €50.000/QALY, the current guideline strategy was most favorable. Sensitivity analyses showed that the combination strategies could be cost-effective if the costs of ctDNA testing are lower than €1500, and/or if ACT is more effective in ctDNA+ than in ctDNA- patients. Improved ctDNA test had limited impact on the cost-effectiveness.

Conclusions

Selecting patients based on ctDNA status in addition to pT4 and MSS status for ACT can improve patient selection in terms of effectiveness, and can also potentially become a cost-effective strategy. However, more research is needed to investigate the prognostic and predictive value of ctDNA to accurately evaluate the (cost)effectiveness.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Amsterdam UMC.

Funding

ZonMW.

Disclosure

G.R. Vink: Financial Interests, Institutional, Sponsor/Funding: BMS, Merck, Servier, Personal Genome Diagnostics, Bayer, Sirtex, Pierre Fabre, Lilly, Delfi Diagnostics. V. Velculescu: Financial Interests, Personal and Institutional, Member of Board of Directors, Stockholder and consultant: Personal Genome Diagnostics, Delfi Diagnostics. G. Meijer: Financial Interests, Personal and Institutional, Member of Board of Directors: CRCbioscreen BV; Financial Interests, Institutional, Research Funding: CZ health insurances; Financial Interests, Institutional, Product Samples, provide materials, equipment and/or sample/genomic analyses: Exact Sciences, Sysmex, Sentinel Ch. SpA, Personal Genome Diagnostics, Delfi, Hartwig Medical Foundation; Other, Personal and Institutional, Other, has several patents pending/issued: Other. D. Van Den Broek: Financial Interests, Institutional, Speaker, Consultant, Advisor: Roche diagnostics. 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, BMS; 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 Farma, Novartis, Merck, Servier, BMS; 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, Institutional, Sponsor/Funding: Bayer, BMS, Merck Serono, Pierre Fabre, Servier, HUB 4 organoids, Cleara Biotech. R. Fijneman: Financial Interests, Institutional, Sponsor/Funding: Cergentis BV, Personal Genome Diagnostics, Delfi Diagnostics, MERCK BV; Other, Personal and Institutional, Other, has several patents pending: Other. V.P. Retel: Financial Interests, Personal and Institutional, Funding: Intuitive BV. All other authors have declared no conflicts of interest.