Chemotherapy for patients with circulating tumour DNA-positive, stage II colon cancer (CIRCULATE): an AIO/ABCSG trial
Background - Adjuvant chemotherapy provides limited benefit in unselected stage II colon cancer. Post-operative circulating tumour DNA (ctDNA) has higher prognostic value than classical clinical markers, with ctDNA positivity indicating an unfavourable outcome. - Patients and methods - Patients with...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
August 2026
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| In: |
Annals of oncology
Year: 2026, Volume: 37, Issue: 8, Pages: 1120-1132 |
| ISSN: | 1569-8041 |
| DOI: | 10.1016/j.annonc.2026.05.001 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.annonc.2026.05.001 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0923753426001808 
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| Author Notes: | G. Folprecht, S. Stasik, A. Reinacher-Schick, L. Weiss, E. Goekkurt, L. Jacobasch, L. Conradi, A. Kröcher, R.-D. Hofheinz, R. Liersch, U.M. Martens, J. Chater, M. Fuchs, J.U. Riera Knorrenschild, J. Schubert, A. Klimova, L. Reinhardt, C. Sperling, J. von Tresckow, J. Weitz, D.E. Aust, A. Tannapfel, J. Christmann & C. Thiede |
| Summary: | Background - Adjuvant chemotherapy provides limited benefit in unselected stage II colon cancer. Post-operative circulating tumour DNA (ctDNA) has higher prognostic value than classical clinical markers, with ctDNA positivity indicating an unfavourable outcome. - Patients and methods - Patients with Union for International Cancer Control stage II, mismatch repair proficient/microsatellite stable colon cancer were tested for ctDNA using an academic, tumour-informed, next-generation sequencing-based test. ctDNA-positive patients were randomly assigned 2:1 to CHEMO (capecitabine ± oxaliplatin) or observation (OBS). ctDNA-negative patients were randomly assigned 1:4 to OBS or OFF-STUDY. ctDNA results were not disclosed in the OBS group. The primary endpoint was disease-free survival (DFS) in ctDNA-positive patients. All differences were tested using one-sided log-rank tests. The trial ended early due to funding expiry. - Results - From June 2020 to July 2025, 2126 patients were screened in Germany and Austria. Overall, 1396 patients (2.9% ctDNA-positive) were randomly assigned: 1083 to OFF-STUDY, 287 to OBS, and 26 to CHEMO, of whom 81% started therapy. DFS and overall survival (OS) were significantly worse in ctDNA-positive versus ctDNA-negative patients [3-year DFS 52% versus 87%, hazard ratio (HR) 4.28, 95% confidence interval (CI) 2.32-7.93, P < 0.001; 3-year OS 88% versus 98%, HR 5.48, 95% CI 1.64-18.28, P = 0.001]. In the intention-to-treat (ITT) cohort, the between-arm differences were not significant (3-year recurrence 36% versus 62%, HR 0.48, 95% CI 0.17-1.33, P = 0.075; 3-year DFS 61% versus 38%, HR 0.55, 95% CI 0.21-1.48, P = 0.12). In the per-protocol analysis (excluding untreated CHEMO patients), time to recurrence and DFS were improved with CHEMO compared with OBS (3-year recurrence 19% versus 62%, HR 0.23, 95% CI 0.06-0.87, P = 0.009; 3-year DFS 77% versus 38%, HR 0.31, 95% CI 0.09-1.03, P = 0.021). - Conclusion - The primary ITT endpoint was not met, potentially related to the reduced power due to premature trial closure. The per-protocol analysis suggests a benefit from adjuvant therapy in ctDNA-positive patients, supporting ctDNA testing for adjuvant decision making in the future. |
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| Item Description: | Online verfügbar: 31. Mai 2026, Artikelversion: 28. Juli 2026 Gesehen am 20.08.2026 |
| Physical Description: | Online Resource |
| ISSN: | 1569-8041 |
| DOI: | 10.1016/j.annonc.2026.05.001 |