Jeanne Tie MD, ESMO Berlin: Liquid Biopsy Brings Chemo-free Option for Patients with Stage Three Colon Cancer

An interview with Jeanne Tie MD, Medical Oncologist, Peter MacCallum Cancer Centre and Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. BERLIN, Germany—Liquid biopsy as a means of monitoring disease control in patients with stage three colon cancer has been investigated in a study from Melbourne, Australia reported to the 2025 Annual Congress of the European Society for Medical Oncology, ESMO. The aim was to discover whether patients with ctDNA negative biopsy findings could safely avoid chemotherapy and be spared toxicities including neuropathy. After reporting findings from the AGITG DYNAMIC-III trial, lead author Jeanne Tie MD, who is a Medical Oncologist at the Peter MacCallum Cancer Centre in Melbourne, Australia, discussed the results with the Audio Journal of Oncology’s reporter, Peter Goodwin: AUDIO JOURNAL OF ONCOLOGY with：Jeanne Tie MD. IN:  “[GOODWIN] I am at the European Society for ….. OUT:  …..Audio Journal of Oncology, I’m Peter Goodwin.  10:20 sec ESMO 2025 ABSTRACT LBA9 (Presidential Symposium): “ctDNA-guided adjuvant chemotherapy de-escalation in stage III colon cancer: Primary analysis of the ctDNA-negative cohort from the randomized AGITG DYNAMIC-III trial (Intergroup study of AGITG and CCTG)” Speaker: Jeanne Tie (Melbourne, Australia, VIC) Authors: Jeanne Tie (Melbourne, Australia, VIC) Yuxuan Wang (Baltimore, United States of America) Jonathan M. Loree (Vancouver, Canada) Joshua Cohen (Baltimore, United States of America) David Espinoza (Camperdown, Australia) Rachel Wong (Box Hill, Australia) Timothy J. Price (Woodville, Australia) Niall Tebbutt (Heidelberg, Australia) Matthew Burge (Herston, Australia) James Lynam (Waratah, Australia) Belinda Lee (Melbourne, Australia) Samuel J. Harris (Bendigo, Australia) Lorraine Chantrill (Wollongong, Australia) Daniel A. Breadner (London, Canada) Christopher O’Callaghan (Kingston, Canada) Chetan Bettegowda (Baltimore, United States of America) Nicholas Papadopoulos (Baltimore, United States of America) Kenneth Kinzler (Baltimore, United States of America) Bert Vogelstein (Baltimore, United States of America) Peter Gibbs (Parkville, Australia) Background Adjuvant chemotherapy (ACT) benefit is uncertain for any individual patient (pt). Post-surgery circulating tumour DNA (ctDNA) testing could support risk-adjusted treatment selection. The DYNAMIC-III study explored ACT de-escalation or escalation, informed by post-surgery ctDNA results. Methods In this multicentre, randomised, phase II/III trial, pts with stage III colon cancer underwent tumour-informed ctDNA testing 5-6 weeks post-surgery and were randomised (1:1) to ctDNA-guided or standard management. Clinicians pre-specified standard ACT. In the ctDNA-guided arm, ctDNA-negative results prompted ACT de-escalation: from 6 to 3 months of fluoropyrimidine (FP) or observation, from 3 months of doublet to single-agent FP, or from 6 months of doublet to 3 months doublet or single-agent FP. The primary endpoint was 3-year recurrence-free survival (RFS). A sample size of 750 provided 80% power with a one-sided 97.5% CI to demonstrate non-inferiority (NI) with a NI margin of 7.5%. Results Of 968 evaluable pts, 702 (72.5%) were ctDNA-negative; 353 assigned to ctDNA-guided and 349 to standard management. Median follow-up was 45 months. 319 (90.4%) pts received ctDNA-guided per-protocol de-escalation. Treatment de-escalation reduced oxaliplatin-based chemotherapy use versus standard management (34.8% vs 88.6%, P < 0.001) and lowered grade 3+ adverse events of special interest (6.2% vs 10.6%, P = 0.037) and treatment-related hospitalisation (8.5% vs 13.2%, P = 0.048). However, non-inferiority of ctDNA-guided de-escalation was not confirmed (3-year RFS, 85.3% vs 88.1%; difference = -2.8%; 97.5% lower CI = -8.0%). Pre-planned subgroup analysis suggested de-escalation may be non-inferior in clinical low-risk (T1-3N1) tumours (3-year RFS, 91.0% vs. 93.2%; difference = -2.2%; 97.5% lower CI = -7.2%). Conclusions Stage III colon cancer pts with negative post-surgery ctDNA had low recurrence risk. ctDNA-guided de-escalation is feasible, substantially reduces oxaliplatin exposure and adverse events, with outcomes approaching standard management, especially for clinical low-risk tumours. Clinical trial identification ACTRN12617001566325 Date registered: 21 November 2017. Legal entity responsible for the study Australasian GastroIntestinal Trials Group (AGITG). Funding Marcus Foundation, NHMRC, Virginia and Ludwig Fund for Cancer Research, Lustgarten Foundation, Conrad R Hilton Foundation, Sol Goldman Charitable Trust, NIH, Eastern Health Research Foundation (Zouki Research Grant), Canadian Cancer Society, Canadian Institutes of Health Research (CIHR).

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