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KOL Pulse — Trial Profile

DYNAMIC-III Trial

Stage III resected colon cancer, ctDNA-guided adjuvant strategy — Australasian Gastro-Intestinal Trials Group (AGITG)

Stage III resected colon cancer, ctDNA-guided adjuvant strategyStrategy trial — no single drugESMO Congress 2025⚠ Negative Trial
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At a Glance

DYNAMIC-III Key Takeaways

Design - Randomized Phase II/III strategy trial by the AGITG with the Canadian Cancer Trials Group (registered ACTRN12617001566325; not on ClinicalTrials.gov): ctDNA-guided adjuvant chemotherapy (de-escalation if ctDNA-negative, escalation if ctDNA-positive) vs standard management in resected stage III colon cancer (ESMO Congress 2025).

Recurrence-free survival (two cohorts) - In the ctDNA-negative (de-escalation) cohort - the primary analysis - 3-year RFS was 85.3% with ctDNA-guided management vs 88.1% with standard care (difference -2.8%; 97.5% lower confidence bound -8.0%, exceeding the 7.5% non-inferiority margin: non-inferiority NOT met). In the separate ctDNA-positive (escalation) cohort, treatment escalation did not improve RFS versus standard chemotherapy (median RFS 29.24 vs 36.8 months; HR 1.11, 90% CI 0.83-1.48). ctDNA-guided de-escalation did reduce oxaliplatin exposure and associated neuropathy.

Overall survival - OS data were not the primary focus of the analysis.

Safety - ctDNA-guided de-escalation reduced oxaliplatin exposure and associated peripheral neuropathy, particularly in low-risk T1-3N1 disease. Grade >=3 AE rates were not detailed in the primary publication.

Regulatory / sponsor - Academic cooperative-group trial (AGITG/CCTG); no regulatory claim. Non-inferiority not met overall, but the trial supports ctDNA-informed personalization: de-escalation is feasible for ctDNA-negative low-risk patients, while ctDNA-positive disease needs strategies beyond chemotherapy intensification.

Compiled and reviewed by the KOL Pulse research team, led by Brian Shields, Founder, KOL Pulse. Last updated August 19, 2026.

Influence Leaders

Top KOLs Discussing DYNAMIC-III

Jun Gong
Jun Gong
@jgong15
26.9K impressions
Arndt Vogel
Arndt Vogel
@ArndtVogel
11.6K impressions
Mario Balsa
Mario Balsa
@MarioBalsaMD
8.9K impressions
Ibrahim Halil SAHIN, MD
Ibrahim Halil SAHIN, MD
@IbrahimSahinMD1
6.5K impressions
Dr Amol Akhade
Dr Amol Akhade
@SuyogCancer
5.3K impressions
Dr. Nina Niu Sanford
Dr. Nina Niu Sanford
@NiuSanford
4.3K impressions
Conference Presentations

DYNAMIC-III Key Slides & Visuals

Official trial slides and relevant visuals shared by KOLs at ESMO Congress 2025. Click any image to expand.

Jun Gong
Jun Gong @jgong15
DYNAMIC-III Data
14K impressions · 38 likes · May 25, 2025
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DYNAMIC-III conference slide — trial design schema and response data: GASTROINTESTINAL CANCER-COLORECTAL AND ANAL
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[Slide 1] GASTROINTESTINAL CANCER-COLORECTAL AND ANAL 3503 Oral Abstract Session ctDNA-guided adjuvant chemotherapy escalation in stage III colon cancer: Primary analysis of the ctDNA-positive cohort from the randomized AGITG dynamic-III trial (intergroup study of AGITG and CCTG). Jeanne Tie, Yuxuan Wang, Jonathan M. Loree, Joshua D. Cohen, David Espinosa, Rachel Wong, Timothy Jay Price, Niall C. Tebbutt, Margaret Lee, Matthew E. Burge, Samuel John Harris, Belinda Lee, James F. Lynam, Christopher J. O'Callaghan, Daniel Adam Breadner, Chetan Bettegowda, Nickolas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein, Peter Gibbs; Department of Medical Oncology, Peter MacCallum Cancer Centre and Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD; BCCA Vancouver Cancer Centre, University of British Columbia, Vancouver, BC, Canada; NHMRC Clinical Trials Centre, Sydney, Australia; Eastern Health, Box Hill, Australia; Queen Elizabeth Hospital, University of Adelaide, Woodville, SA, Australia; Warringal Private Hospital, Melbourne, Australia; Eastern Health, Western Health, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia; Royal Brisbane and Women's Hospital, Herston, QLD, Australia; Bendigo Cancer Centre, Bendigo Health, Bendigo, VIC, Australia; Northern Health & Peter MacCallum Cancer Centre & Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia; Newcastle Private Hospital, Newcastle, Australia; Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada; Verspeeten Family Cancer Centre at the Schulich School of Medicine and Dentistry, London, ON, Canada; Johns Hopkins University School of Medicine, Baltimore, MD; Walter & Eliza Hall Institute of Medical Research and Western Health, Melbourne, Australia Background: Despite adjuvant chemotherapy (ACT) a proportion of patients (pts) with stage III colon cancer (CC) will recur. Most at risk are those with detectable ctDNA, whereas those with undetectable ctDNA have a reduced recurrence risk. The DYNAMIC-III study explored the impact of ACT de-escalation or escalation as informed by post-surgery ctDNA results. Here, we report the primary analysis on the impact of treatment escalation in ctDNA-positive pts. Outcome data for treatment de-escalation in ctDNA-negative pts is immature. Methods: DYNAMIC-III is a multi-center, randomized, phase II/III trial. Eligible pts had resected stage III CC and were fit for ACT. Pts were randomly assigned 1:1 to ctDNA-informed or standard of care (SOC) management. Clinicians nominated the selected SOC ACT regimen prior to ran- domization. For ctDNA-informed management, a ctDNA-positive result at 5-6 weeks after surgery with a tumor-informed assay prompted an escalation ACT strategy (from single agent fluoropyrimidine [FP] to oxaliplatin-based doublet, from 3 months doublet to 6 months doublet or FOLFOXIRI [clinician choice], or from 6 months doublet to FOLFOXIRI). The primary efficacy endpoint for the ctDNA-positive cohort was 2-year RFS. The target sample size of 250 provided 80% power with 90% confidence to confirm superiority of ctDNA-informed treat- ment escalation compared to SOC with a HR of 0.746. Results: Of 961 eligible pts randomized between Oct 2017 and Apr 2023, 259 (27%) were ctDNA-positive. Of these, 113 (44%) had clinical low risk disease (non-N2 + non-T4). Median follow-up was 42.2 months (range 0.78 - 63.0). 115 (89%) of 129 ctDNA-informed pts received ACT escalation, with 65 (56%) receiving FOLFOXIRI. Of 130 SOC pts, 14 (11%) and 112 (86%) received single agent FP and oxaliplatin doublet, respectively. 2-year RFS for ctDNA-informed treatment escalation was 52% (90% CI: 44 - 59%) vs 61% (90% CI: 54 68%) for SOC (HR 1.11, 90% CI: 0.83 1.48; P = 0.6). The 3-year RFS for ctDNA-positive pts receiving FOLFOXIRI and FOLFOX/CAPOX was similar (47% vs 51%, HR 1.09, 90% CI 0.78 to 1.53; P = 0.7). In a pre-specified correlative analysis of all ctDNA positive pts, recurrence risk increased with ctDNA burden, with 3-year RFS of 78%, 63%, 36% and 22% for tumor-derived mutant molecules/mL quartiles < 0.06, 0.06 - 0.17, 0.18 - 1.31, and > 1.31, respectively (P < 0.01). Treatment-related hospitalisation was similar for escalated and SOC pts (OR 1.21, P = 0.58). Analysis of post-ACT ctDNA is underway. Conclusions: In this first randomised study of ctDNA-informed management in stage III CC, we confirm the prognostic significance of detectable ctDNA, with the novel finding of recurrence risk increasing markedly with ctDNA burden. Treatment escalation, including to FOLFOXIRI, did not improve RFS. Future studies in ctDNA positive pts should explore other escalation strategies. Clinical trial infor- mation: ACTRN12617001566325. Research Sponsor: Marcus Foundation; NHMRC; U.S. National Institutes of Health.
Jun Gong
Jun Gong @jgong15
DYNAMIC-III Data
12.5K impressions · 29 likes · May 30, 2025
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DYNAMIC-III conference slide — trial design schema and Kaplan-Meier survival data: ctDNA-Guided Adjuvant Chemotherapy
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DYNAMIC-III conference slide — trial design schema and Kaplan-Meier survival data: ctDNA-Guided Adjuvant Chemotherapy
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DYNAMIC-III conference slide — trial design schema and Kaplan-Meier survival data: ctDNA-Guided Adjuvant Chemotherapy
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DYNAMIC-III conference slide — trial design schema and Kaplan-Meier survival data: ctDNA-Guided Adjuvant Chemotherapy
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[Slide 1] ctDNA-Guided Adjuvant Chemotherapy Escalation in Stage III Colon Cancer : statistical concerns No formal hypotheses HO and H1 as usually in non The NEW ENGLAND JOURNAL of MEDICINE comparative randomized phase II trials ORIGINAL ARTICLE Randomized non-comparative phase II but Oxaliplatin, Fluorouracil, and Leucovorin as Adjuvant Treatment for Colon Cancer comparisons are provided 10 0.9 FL plus examplation (237 events, 21 1%) How can we target a HR of 0.746 with only 250 pts? 0.0 case free Survival 0.7 FL (293 events 26 293 0.6 Underpowered : for the targeted HR of 0.746 a n.e. In MOSAIC 2200+ pts power of 37% was expected (???) for a 5% difference in 3-y DFS and an HR of 0.78 Conclusions are at most hypothesis generating 0 5 12 :$ 24 10 34 42 48 Months No. at Risk FLe oxaliplatin 1123 1086 1021 959 *** 663 395 FL 1123 1006 981 903 817 619 156 MOSAIC trials (NEJM 204) 2025 ASCO #ASCO25 PRI SENTED BY: Julien TAIEB, MD, PhD ASCO AMERICAN SOCIETY OF CLINICAL ONCOLDGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for - contact permissions@asco.org KNOWLEDGE CONQUERS CANCER --- [Slide 2] ctDNA-Guided Adjuvant Chemotherapy Escalation in Stage III Colon Cancer :Main results Recurrence free survival Is it acceptable to do this comparison? 1.0 No randomization of CT regimen 0.8 Why FOLFOXIRI 3 to 6 M and not 6M ? FOLFOX/CAPOX 0.6 51% CAPOX and FOLFOX: high and low-risk patients FOLFOXIRI FOLFOXIRI high-risk patients only 0.4 47% 0.2 HR 1.09 (0.78, 1.53), P = 0.662 TDMM/mL, median (IQR) P FOLFOXIRI 0.28 (0.06, 1.78) 0.236 0.0 0 6 12 18 24 30 36 12 IS Doublet 0.15 (0.06, 0.97) Time from randomisation - Months FOLFOXIRI 65 64 62 57 51 ++ 36 32 30 19 23 22 20 19 1" 16 IS Doubles 169 16-4 156 144 134 120 103 96 76 67 60 53 47 45 40 35 33 Imbalance in baseline characteristics 2025 ASCO #ASCO25 PRESENTEDUARION TAIEB, MD, PhD ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation # property of the author and ASCO Temasure required for - contact Causing KNOWLEDGE CONQUERS CANCER --- [Slide 3] ctDNA-Guided Adjuvant Chemotherapy Escalation in Stage III Colon Cancer :my conclusions Altogether DYNAMIC confirms that "when it goes bad it goes bad" Escalation in ctDNA positive patients is inefficient to improve RFS in DYNAMIC FOLFOXIRI and CAPOX/FOLFOX groups were not randomized and lets wait for the IROCAS-PRODIGE-GONO-CCTG study results next year (FOLFIRINOX vs FOLFOX in T4/N2 cc) High number attrition for ctDNA clearance makes results more hypothesis generating than conclusive 2025 ASCO #ASCO25 PRI SENTECULATION TAIEB, MD, PhD ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for revie, contact permissore@asco.org KNOWLEDGE CONQUERS CANCER --- [Slide 4] ctDNA-Guided Adjuvant Chemotherapy Escalation in Stage III Colon Cancer :my conclusions However these results, though not completely conclusive, suggest that: ctDNA clearance post treatment may be a potential new primary endpoint in future trials ACCENT-CIRCULATE working group for confirmatory pooled analyses We need more than chemotherapy intensification to improve outcome in stage III CC patients 20 years after the publication of MOSAIC PLATFORM TRIALS WITH NEW TREATMENT OPTION and NEW TREATMENT STRATEGIES New treatments (targeted agents, ADCs, ICIs) and New treatment strategies (neo-adjuvant, sequential or even both 2025 ASCO #ASCO25 TAIEB, MD. PhD ASCO AMERICA AN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation a property of the author and ASCO Permission required for - consect permissions@ass.org KNOWLEDGE CONQUERS CANCER
Arndt Vogel
Arndt Vogel @ArndtVogel
DYNAMIC-III Data
11.6K impressions · 80 likes · May 30, 2025
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DYNAMIC-III conference slide — trial design schema: Recurrence-Free Survival
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DYNAMIC-III conference slide — trial design schema: DYNAMIC-III Study Design
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DYNAMIC-III conference slide — trial design schema: Post-Op ctDNA Molecular Burden and RFS
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DYNAMIC-III conference slide — trial design schema: Post-Hoc Analysis: FOLFOXIRI VS FOLFOX/CAPOX
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[Slide 1] Recurrence-Free Survival 1.0 Median 0.8 Total RFS 2-year RFS 3-year RFS Events (90% CI) (90% CI) (mths) 61% 52% 48% 0.6 ctDNA 129 66 29.24 52% (44, 59) (40, 55) 61% 52% 52% SoC 130 62 36.80 0.4 48% (54,68) (44, 60) HR (90% CI): 1.11 (0.83, 1.48), P = 0.57 0.2 — Standard management Median follow-up 42.2 months (0.78 - 63.0) - ctDNA-informed escalation 00 0 6 12 18 24 30 36 42 48 Time from randomisation - - Months ctDNA-Informed 129 123 118 109 101 90 76 68 55 52 42 38 33 32 28 26 25 Standard 130 126 120 111 101 91 79 74 63 54 50 44 40 37 34 30 28 Data cut-off: 14 Nov 2024 2025 ASCO #ASCO25 PRE SENTED BY: Jeanne Tie, MBChB FRACP MD ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER --- [Slide 2] DYNAMIC-III Study Design Randomized Phase 11/111 (ACTRN12617001566325) Tumor-Informed Stage III ctDNA Analysis ctDNA-Informed Management Pre-Planned SoC Escalation Colon Cancer (SaferSeqS¹ targeted CRC panel) ctDNA-Negative De-escalate R0 resection No chemotherapy 5FU/Cape ECOG 0 - 2 ctDNA-Positive Escalate 5FU/Cape 6M Oxaliplatin doublet Fit for at least a fluoropyrimidine (FP) 1 cycle of pre-planned chemotherapy allowed R 3M Oxaliplatin doublet 6M Doublet prior to ctDNA-informed regimen Staging CT within 12 W5-6 1:1 or ≥ 3M FOLFOXIRI weeks Provision of 6M Oxaliplatin doublet ≥ 3M Standard Management adequate tumor FOLFOXIRI Clinicians tissue < 6 weeks nominate Treatment per clinician's choice post-operation SoC Chemo (blinded to ctDNA result) No synchronous colorectal cancer Stratified by clinical risk (low VS high) and sites Primary Analysis of ctDNA-Positive Cohort: Endpoints to be Presented Secondary: safety, end-of-treatment (EoT) ctDNA clearance Primary: 2 years RFS Exploratory: post-operative ctDNA levels 1. Cohen, J.D. et al. Nat Biotechnol 39, 1220-1227 (2021) 2025 ASCO #ASCO25 PRE SENTED BY: Jeanne Tie, MBChB FRACP MD ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER --- [Slide 3] Post-Op ctDNA Molecular Burden and RFS RFS: ctDNA Burden by Quartiles TDMM / mL RFS HR (90% CI) P ≥1.31 1 <.0001 1.0 0.18-1.31 0.65 (0.46, 0.93) 83% 0.06-0.17 0.26 (0.17, 0.39) 78% 0.8 TDMM <0.06 <0.06 0.17 (0.10, 0.27) 74% TDMM 0.06-0.17 0.6 63% 43% 0.4 36% TDMM 0.18-1.31 26% TDMM >1.31 0.2 22% 00 0 6 12 18 24 30 36 42 48 Time from randomisation - Months 1 64 56 52 43 36 29 21 19 14 14 11 10 9 8 8 7 6 2 64 62 58 51 42 36 30 28 21 19 15 14 11 11 11 8 6 3 67 67 66 64 63 57 51 47 41 36 32 27 25 24 23 23 23 4 64 64 62 62 61 59 53 48 42 37 34 31 28 26 20 18 18 TDMM = Tumor derived mutant molecule 2025 ASCO #ASCO25 PRE SENTED BY: Jeanne Tie, MBChB FRACP MD ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER --- [Slide 4] Post-Hoc Analysis: FOLFOXIRI VS FOLFOX/CAPOX Recurrence free survival TDMM/mL, median (IQR) P FOLFOXIRI 0.28 (0.06, 1.78) 0.236 1.0 Doublet 0.15 (0.06, 0.97) 0.8 ctDNA Clearance Rate by Regimen FOLFOX/CAPOX ns 0.6 51% 100 FOLFOXIRI Clearance 0.4 47% 80 No Clearance 0.2 EoT ctDNA Status (%) 60 HR 1.09 (0.78, 1.53), P = 0.662 40 0.0 60% 62% 0 6 12 18 24 30 36 42 48 20 (31/52) (47/76) Pause Time from randomisation - Months POLPOXIRI 65 64 62 57 51 44 36 32 30 29 23 22 20 19 17 16 15 0 Doublet 169 164 156 144 134 120 103 96 76 67 60 53 47 45 40 35 33 FOLFOXIRI Doublet 2025 ASCO #ASCO25 PRE SENTED BY: Jeanne Tie, MBChB FRACP MD ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER
Mario Balsa
Mario Balsa @MarioBalsaMD
DYNAMIC-III Data
8.5K impressions · 74 likes · Oct 20, 2025
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DYNAMIC-III conference slide — trial design schema and Kaplan-Meier survival data: DYNAMIC-III Study Design
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DYNAMIC-III conference slide — trial design schema and Kaplan-Meier survival data: Recurrence-Free Survival
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DYNAMIC-III conference slide — trial design schema and Kaplan-Meier survival data: RFS by Clinical Risk
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DYNAMIC-III conference slide — trial design schema and Kaplan-Meier survival data: ctDNA-Negative vs ctDNA-Positive: RFS
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[Slide 1] DYNAMIC-III Study Design Randomised Phase II/III (ACTRN12617001566325) Stage III ctDNA-Informed Management Colon Cancer ctDNA-Negative De-escalate R0 resection ctDNA-Positive Escalate ECOG 0-2 - Fit for at least a 1 cycle of pre-planned chemotherapy allowed prior to fluoropyrimidine (FP) R ctDNA-informed regimen Staging CT within 12 W5-6 1:1 weeks Provision of adequate Standard Management tumor tissue <6 weeks post-operation Treatment per clinician's choice No synchronous (blinded to ctDNA result) colorectal cancer Stratified by clinical risk (low VS high) and sites Jeanne Tie Content of this presentation is copyright and responsibility of the author Permission is required for re-use 1. Cohen, J.D. et al. Nat Biotechnol 39, 1220-1227 (2021) BERLIN 2025 ESMO congress --- [Slide 2] Recurrence-Free Survival Median follow-up 47 months (0.68 - 67.0) 100 88.1 Arm Total Events 90 Standard 3-year RFS (95% CI) 80 85.3 ctDNA 353 63 85.3% (81, 89) ctDNA-guided 70 Recurrence-free Survival (%) Standard 349 45 88.1% (84, 91) 60 50 40 Absolute Difference in 3-year RFS (95% CI) 30 20 Absolute difference -2.8% 10 (95% CI, -8.0% to 2.3%) -8.0% 0 0 12 24 36 48 60 Months from Randomization No. at Risk ctDNA-guided 353 333 303 214 124 51 -10.0 -7.5 -5.0 -2.5 0 2.5 Standard 349 336 310 223 143 46 Standard better ctDNA-guidance better Jeanne Tie Database lock July 29, 2025 Content of this presentation is copyright and responsibility of the author Permission is required for re-use BERLIN 2025 ESMO congress --- [Slide 3] RFS by Clinical Risk Clinical Low Risk (T1-3N1) Clinical High Risk (T4 and/or N2) 100 93.2 Standard 100 90 90 91.0 78.6 80 ctDNA-guided 80 Standard 70 70 Recurrence-free Survival (%) 60 40 30 Recurrence-free Survival (%) 72.8 60 ctDNA-guided 50 50 40 30 20 20 10 Absolute difference -2.2% (95% CI, -7,2% to 2.7%) 10 Absolute difference -5.8% (95% CI, -17.0% to 5.4%) 0 0 0 12 24 36 48 60 0 12 24 36 48 60 Time from Randomization (months) Time from Randomization (months) No. at Risk No. at Risk tDNA-guided 242 233 219 160 93 39 ctDNA-guided 111 100 84 54 31 12 Standard 227 222 209 152 95 32 Standard 122 114 101 71 48 14 Jeanne Tie Content of this presentation is copyright and responsibility of the author Permission is required for re-use BERLIN 2025 ESMO congress --- [Slide 4] ctDNA-Negative vs ctDNA-Positive: RFS 100 87 RFS by ctDNA Molecular Burden (Quartiles) 90 0 TDMM 77 80 0<TDMM<0.06 TDMM / mL RFS HR (90% CI) P 70 60 Recurrence-free Survival (%) 0.06-0.17 TDMM ≥1.31 1 <.0001 60 50 0.18-1.31 0.67 (0.47, 0.94) . . 40 37 0.18-1.31 TDMM 0.06-0.17 0.28 (0.19, 0.42) - 30 23 >1.31 TDMM >0 to <0.06 0.17 (0.10, 0.27) . 20 10 0 (ctDNA-negative) 0.10 (0.07, 0.13) . 0 TDMM = Tumour derived mutant molecule 0 12 24 36 48 60 e a C . S Γ Months from Randomization No. at Risk >1.31 TDMM 64 36 17 12 8 3 0.18-1.31 TDMM 64 42 25 16 10 3 0.06-0.17 TDMM 67 63 48 32 24 10 0<TDMM<0.06 64 61 52 34 22 6 0 TDMM 702 669 613 437 267 97 Jeanne Tie Content of this presentation is copyright and responsibility of the author. Permission is required for re-use BERLIN ESMO congress
Suneel Kamath MD
Suneel Kamath MD @SKamath_MD
DYNAMIC-III Data
3.7K impressions · 18 likes · May 30, 2025
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DYNAMIC-III conference slide — trial design schema: ctDNA-Guided Adjuvant Chemotherapy Escalation in
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DYNAMIC-III conference slide — trial design schema: CtDNA is an amazing tool
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[Slide 1] ctDNA-Guided Adjuvant Chemotherapy Escalation in Stage III Colon Cancer :Main results Recurrence free survival 1.0 Primary endpoint is not reached 0.8 61% 0.6 52% 52% 0.4 48% HR (90% CI): 1.11 (0.83, 1.48), P = 0.57 0.2 - Standard management - ctDNA-informed escalation 00 0 6 12 18 24 30 36 42 48 Time from randomisation - Months ctDNA Informed 129 123 118 109 101 90 76 68 55 52 42 38 33 32 28 26 25 Standard 130 126 120 111 101 91 79 74 63 54 50 44 40 37 34 30 28 2025 ASCO #ASCO25 PRESENTED BY: Julien TAIEB, MD. PhD ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation . property of the author and ASCO Permission required for - contact permissions@asco.org KNOWLEDGE CONQUERS CANCER --- [Slide 2] Limitations CtDNA is an amazing tool - but it didn't make FOLFOX more effective Lead time bias Limitations of detection - By tumor site: peritoneum, lung, low tumor burden - Types of alterations: fusions and amplifications (e.g. 15-20% false negative rate for HER2 amplification) Technical Failure: May be as high as 15% in clinical practice Cost: Upfront cost with likely downstream cost-savings Patient anxiety
Community Discussion

DYNAMIC-III Top Tweets

Top tweets by impressions — click to view on X

Jun Gong
Jun Gong@jgong15

Lot of discussion to surely follow the DYNAMIC-III #ASCO25 oral. For rand trials of ctDNA-guided adj therapy in colon cancer to date:

➕trials
DYNAMIC, CALGB 80702 (post-hoc)

➖DYNAMIC III, ALTAIR,…

👁 14K ♡ 38 ↻ 12 May 25, 2025
Jun Gong
Jun Gong@jgong15

Dr. Taken discussant w/insight into DYNAMIC-III, underpowered for target HR 0.746 w/n=250 pts (MOSAIC needed &gt;2200 pts for HR 0.78), heterogeneity in FOLFOXIRI duration. A power of 37% makes…

👁 12.5K ♡ 29 ↻ 17 May 30, 2025
Arndt Vogel
Arndt Vogel@ArndtVogel

ctDNA-guided adj CTx escalation in stage III CRC
#ASCO25
🔎Primary analysis of the ctDNA-positive cohort from the randomized AGITG DYNAMIC-III trial
👉mRFS 29 vs 36 mo
👉CTx escalation does not improve…

👁 11.6K ♡ 80 ↻ 36 May 30, 2025
Mario Balsa
Mario Balsa@MarioBalsaMD

💎 #ESMO25 Presidential Session w/ @JeanneTie #ColorectalCancer – Phase III DYNAMIC-III: ctDNA-guided de-escalation after surgery in stage III colon cancer

In ctDNA⁻ patients:
☄️ 3-year RFS 85.3%…

👁 8.5K ♡ 74 ↻ 33 Oct 20, 2025
Dr. Nina Niu Sanford
Dr. Nina Niu Sanford@NiuSanford

DYNAMIC III: another study showing ctDNA prognostic, but not predictive.

At this point, the main scenario I see for ctDNA guiding treatment decision making in CRC is potentially selecting patients…

👁 4.3K ♡ 34 ↻ 6 May 30, 2025
Ibrahim Halil SAHIN, MD
Ibrahim Halil SAHIN, MD@IbrahimSahinMD1

Very interesting data❗️

✳️Some sobering facts but few things important to note here:

👉ctDNA assays used in these studies matter. We have seen this in COBRA trial.
👉The study allowed optional…

👁 4.1K ♡ 13 ↻ 9 May 25, 2025
Dr Amol Akhade
Dr Amol Akhade@SuyogCancer

📢 #ASCO25 GI – DYNAMIC-III Trial
🧬 Can escalation of chemo overcome ctDNA+ risk in stage III colon cancer?
🧪 Design:
961 pts randomized to:
➡️ ctDNA-informed ACT escalation
➡️ Standard ACT (SOC)
📈…

👁 3.8K ♡ 20 ↻ 6 May 22, 2025
Suneel Kamath MD
Suneel Kamath MD@SKamath_MD

DYNAMIC-III study shows no benefit of giving more chemo for ctDNA+ stage 3 colon cancer.

I always say, ctDNA is amazing and cool, but it doesn&#x27;t make FOLFOX (or irinotecan) more effective. #ASCO25…

👁 3.7K ♡ 18 ↻ 4 May 30, 2025
Van Morris, MD
Van Morris, MD@VanMorrisMD

❔ ctDNA detection is PROGNOSTIC for inferior outcomes following resection of stage III colon cancer, but is treating more aggressively better?

‼️ NO improvement in RFS by escalating treatment with a…

👁 3.3K ♡ 64 ↻ 21 May 30, 2025
Oncology Brothers
Oncology Brothers@OncBrothers

4. #DYNAMIC: ctDNA to escalate treatment in Stage III colon cancer.

- Post-surgery, ctDNA+ is high: 3 yrs recurrence risk RFS ~50%.
- FOLFOXIRI (escalation) didn’t reduce risk: 2-yr RFS 52% vs…

👁 3.2K ♡ 11 ↻ 5 May 30, 2025
Trial Background

About the DYNAMIC-III Trial

Overall non-inferiority not met, but trial supports ctDNA-informed personalization. De-escalation is feasible for ctDNA-negative low-risk patients. ctDNA-positive disease needs novel strategies beyond chemo intensification.

📄 AGITG DYNAMIC-III (ACTRN12617001566325) 📄 Pivotal Publication
Study Design

Trial Methodology & Results

Recurrence-Free Survival (RFS) — Primary Endpoint (Non-Inferiority)

In the ctDNA-negative (de-escalation) cohort — the primary analysis — 3-year RFS was 85.3% with ctDNA-guided management vs. 88.1% with standard care (difference -2.8%, 97.5% lower confidence bound -8.0%, exceeding the 7.5% non-inferiority margin: non-inferiority NOT met). In the separate ctDNA-positive (escalation) cohort, treatment escalation did not improve RFS (median RFS 29.24 vs. 36.8 mo; HR 1.11, 90% CI 0.83-1.48).

⚠️ Non-inferiority NOT met (HR 1.11)

📄 Source: KOL commentary on X →

Overall Survival (OS)

OS data were not the primary focus of the analysis. ctDNA-guided de-escalation reduced oxaliplatin exposure and associated neuropathy, particularly in low-risk T1-3N1 disease.


📄 Source →

Safety & Tolerability

De-escalation arm reduced oxaliplatin exposure and associated peripheral neuropathy. Specific Grade ≥3 AE rates were not detailed in the primary publication; the key safety signal is favorable toxicity reduction with de-escalation.

✓ Reduced oxaliplatin exposure with de-escalation

📄 Source →

Clinical Implications

⚠️ Non-inferiority not met — but practice-informing for ctDNA-informed personalization. Overall non-inferiority not met, but trial supports ctDNA-informed personalization. De-escalation is feasible for ctDNA-negative low-risk patients. ctDNA-positive disease needs novel strategies beyond chemo intensification.

Frequently Asked Questions

DYNAMIC-III FAQ

What is the DYNAMIC-III trial?

DYNAMIC-III is a randomized Phase II/III strategy trial run by the Australasian Gastro-Intestinal Trials Group (AGITG) with the Canadian Cancer Trials Group, testing whether circulating tumor DNA (ctDNA) results after surgery can guide adjuvant chemotherapy intensity in resected stage III colon cancer. ctDNA-negative patients were de-escalated and ctDNA-positive patients were escalated, versus standard management. Results were presented at ESMO Congress 2025.

What did DYNAMIC-III show?

In the ctDNA-negative (de-escalation) cohort - the primary analysis - 3-year RFS was 85.3% with ctDNA-guided management vs 88.1% with standard care (difference -2.8%; 97.5% lower confidence bound -8.0%, exceeding the 7.5% non-inferiority margin: non-inferiority NOT met). In the separate ctDNA-positive (escalation) cohort, treatment escalation did not improve RFS versus standard chemotherapy (median RFS 29.24 vs 36.8 months; HR 1.11, 90% CI 0.83-1.48). ctDNA-guided de-escalation did reduce oxaliplatin exposure and associated neuropathy.

Is any drug FDA approved based on DYNAMIC-III?

No, and none was expected to be - DYNAMIC-III is an academic treatment-strategy trial, not a drug-registration trial. It tested how to deploy already-standard adjuvant chemotherapy regimens using ctDNA guidance, so there is no associated FDA approval claim.

What is the safety takeaway from DYNAMIC-III?

The de-escalation strategy reduced oxaliplatin exposure and its associated peripheral neuropathy, particularly in low-risk T1-3N1 disease. Specific Grade >=3 adverse event rates were not detailed in the primary publication; the key safety signal is favorable toxicity reduction with ctDNA-guided de-escalation.

Why is DYNAMIC-III important despite being a negative trial?

Although overall non-inferiority was not met, DYNAMIC-III is practice-informing for ctDNA-guided personalization in colon cancer. It suggests de-escalation is feasible for ctDNA-negative low-risk patients, while ctDNA-positive disease appears to need novel strategies beyond chemotherapy intensification.

Major Media & Publications

DYNAMIC-III in the News

Publication
DYNAMIC-III: ctDNA-guided adjuvant chemotherapy de-escalation in stage III colon cancer
PubMed2025
 Media Coverage
Postsurgical ctDNA Testing in Stage III Colon Cancer for Treatment De-escalation
The ASCO Post2025-11-25
 Media Coverage
DYNAMIC-III ctDNA Colon Cancer — Summary
Oncodaily Oncolibrary2025
 Press Release
DYNAMIC-III trial results
AGITG / GI Cancer Australia2025
 Media Coverage
ctDNA-Guided Adjuvant Chemo De-escalation Reduces Toxicity with Comparable Outcomes
ecancer2025
Physician Opinions

Key KOL Sentiments — DYNAMIC-III

DoctorSentimentComment
Dr Amol Akhade ● POSITIVE 📢 #ASCO25 GI – DYNAMIC-III Trial 🧬 Can escalation of chemo overcome ctDNA+ risk in stage III colon cancer? 🧪 Design: 961 pts randomized to: ➡️ ctDNA-informed ACT escalation ➡️ Standard ACT (SOC) 📈 Results (ctDNA+ pts) 2y RFS: Escalation: 52% SOC: 61% HR 1.11 | ❌ Not
ilyas sahin, MD ● POSITIVE The DYNAMIC-III trial showed that using circulating tumor DNA (ctDNA) after surgery can safely reduce chemotherapy use in stage III colon cancer patients who test ctDNA-negative, while intensifying treatment for ctDNA-positive patients did not improve outcomes. @NatureMedicine https://t.co/7nOxIElb1f
Mario Balsa ● POSITIVE The DYNAMIC-III trial did not formally meet non-inferiority for ctDNA-negative patients, so no immediate change in practice YET. Still, for me, these are very encouraging data supporting a more tailored adjuvant approach💡
Paula Jimenez Fonseca ● POSITIVE #ESMO25 | DYNAMIC-III ▶️Stage III CCR, ctDNA− post-operative guided adjuvant CT. De-escalation (oxaliplatin use 35 vs 89%); fewer G≥3 AEs ▶️3yearRFS 85 vs 88% -non-inferiority not met, but ~ outcomes, esp. low-risk (T1–3N1)🩺 Supports safe de-escalation and less overtreatment🌿
Michael Shusterman, MD ● POSITIVE @jgong15 @GIMedOnc @OncoAlert @IbrahimSahinMD1 @ASCO @GIcancerDoc @benweinbergmd @jonathan_nowak @NVijayvergiaMD @Jcj84Jeremy @aparna1024 @Ahn_Daniel_Onc @DrR_DUNNE @mgfakih @AnwaarSaeed3 @GarridoLagunaMD @OncBrothers @DrKatePedersen @sepideh_gholami @AGangiMD @cancerassassin1 @smitha42 I think likely the benefit here is in de-escalation opportunities. We probably will find patients who will not benefit, but I am not sure that throwing the proverbial kitchen sink of more cytotoxics is going to cure a higher proportion of ctDNA positive patients.
Daisuke Kotani, MD, Ph.D 小谷 大輔 ● POSITIVE LBA9: DYNAMIC-III, ctDNA-guided adjuvant de-escalation strategy in ctDNA- stage III colon cancer ✅Of 968 patients, 702 (72.5%) were ctDNA- ✅Non-inferiority margin: 7.5% ✅3-year RFS: 85.3% vs 88.1%, 97.5% lower CI = -8.0% (primary endpoint not met) ✅3-year RFS: 91.0% vs 93.2%,
Jun Gong ● NEUTRAL Lot of discussion to surely follow the DYNAMIC-III #ASCO25 oral. For rand trials of ctDNA-guided adj therapy in colon cancer to date: ➕trials DYNAMIC, CALGB 80702 (post-hoc) ➖DYNAMIC III, ALTAIR, COBRA Where do we go from here? @OncoAlert @IbrahimSahinMD1 @guildsman @ASCO https://t.co/psdUyvgDi2
Arndt Vogel ● NEUTRAL ctDNA-guided adj CTx escalation in stage III CRC #ASCO25 🔎Primary analysis of the ctDNA-positive cohort from the randomized AGITG DYNAMIC-III trial 👉mRFS 29 vs 36 mo 👉CTx escalation does not improve outcome 🧐 ctDNA very helpful to understand risk groups, but we need better https://t.co/HS5M9xzjqA
Mario Balsa ● NEUTRAL 💎 #ESMO25 Presidential Session w/ @JeanneTie #ColorectalCancer – Phase III DYNAMIC-III: ctDNA-guided de-escalation after surgery in stage III colon cancer In ctDNA⁻ patients: ☄️ 3-year RFS 85.3% vs 88.1% (standard) 🎯 Oxaliplatin exposure reduced 88.6% ➜ 34.8% 💥 Fewer https://t.co/4V5OLJ8Xbd
Dr. Nina Niu Sanford ● NEUTRAL DYNAMIC III: another study showing ctDNA prognostic, but not predictive. At this point, the main scenario I see for ctDNA guiding treatment decision making in CRC is potentially selecting patients for non-operative management after chemo/chemoRT in rectal cancer. https://t.co/RLqX1IkOow
Ibrahim Halil SAHIN, MD ● NEUTRAL Very interesting data❗️ ✳️Some sobering facts but few things important to note here: 👉ctDNA assays used in these studies matter. We have seen this in COBRA trial. 👉The study allowed optional escalation to folfoxiri (physician choice) which is a bit problematic. In NRG-GI008, https://t.co/e01w8RLVoN
Van Morris, MD ● NEUTRAL ❔ ctDNA detection is PROGNOSTIC for inferior outcomes following resection of stage III colon cancer, but is treating more aggressively better? ‼️ NO improvement in RFS by escalating treatment with a ctDNA-informed approach. Congrats to DYNAMIC-III study team for highly https://t.co/E31awzt0l3
Oncology Brothers ● NEUTRAL 4. #DYNAMIC: ctDNA to escalate treatment in Stage III colon cancer. - Post-surgery, ctDNA+ is high: 3 yrs recurrence risk RFS ~50%. - FOLFOXIRI (escalation) didn’t reduce risk: 2-yr RFS 52% vs 61%. - ctDNA clearance tied to better outcomes (3-yr RFS 84% vs 12%). Future 5/6 https://t.co/xWTHGPt2Xk https://t.co/WuZbOUevWl
Yakup Ergün ● NEUTRAL #ASCO25 DYNAMIC-III: ctDNA-guided adjuvant chemo escalation in stage III colon cancer 2y RFS ➡️ 52% (escalation) vs 61% (SOC) 3y RFS ➡️ 47% (FOLFOXIRI) vs 51% (doublet) HR ➡️ 1.11 (p=0.6) ctDNA is prognostic—but still not predictive (yet). We know who's at risk, but not yet who https://t.co/D6VWVmu3v8
Erman Akkus ● NEUTRAL 👑DYNAMIC-III ctDNA(-) cohort Presidential 3 #ESMO25 @myESMO ➡️ctDNA-guided adjuvant ChT de-escalation in stage-III colon cancer ✅de-escalation may be non-inferior in clinical low-risk (T1-3N1) tumours #cancer #oncology #MedX @OncoAlert https://t.co/9cF5G0G1ua
M. Bolton ● NEUTRAL 🚨 🚨 ‼️ DYNAMIC-III RCT Resected stage III colon cancer -&gt; R 1:1 to ctDNA-informed or standard of care (SOC) 2y RFS for ctDNA-informed tx esc was 52% v 61% for SOC! HR 1.11 (0.9 CI 0.83-1.48) More data to embarrass ctDNA, what a failure! https://t.co/aj92zWH14w
Oriol Mirallas MD ● NEUTRAL 🚀 LAST Presidential III #ESMO25 🩸Excited for another #ctDNA trial🤩 🫴🏽 DYNAMIC-III trial: De-escalate Chemo in #ctDNA neg stage III #CRC 🗣️ @JeanneTie ❌ mDFS Non-inferiority NOT met ⬇️ Oxalis 88--&gt;34% ☣️ Better TRAE with de-escalation @OncoAlert @myESMO @ASCO @_SEOM https://t.co/x7DIXKfbTc
Dr Amol Akhade ● NEUTRAL Dynamic III study in CRC . Full abstract below and check the analysis in tweet below 🙂👇 @ASCO @NiuSanford @ajumathew_ #ASCO25 https://t.co/YpR6StFWd2 https://t.co/CrnsOHGtxq
Daisuke Kotani, MD, Ph.D 小谷 大輔 ● NEUTRAL ctDNA-guided de-escalation was associated with impaired efficacy for T4 and/or N2. For T1-3N1, it worked well, with only a 2.2% RFS difference at 36 months, though KM curve tails separated slightly after 36 months. For example, a 2-3% difference at 36 months may be negligible https://t.co/tDnOG8X5ki
Oncology Brothers ● NEUTRAL 3. #DYNAMICIII: ctDNA in guiding Adj treatment in high risk Stage II and Stage III Colon Ca: - ctDNA resulted in decrease use of Oxali. - ctDNA remains a good prognostic tool. - Non-inferiority to SoC NOT confirmed - How are you using this today outside trials? @GIMedOnc 5/10 https://t.co/nThbO9zR5M https://t.co/JbY3Z4m0Ec
Jun Gong ● NEGATIVE Dr. Taken discussant w/insight into DYNAMIC-III, underpowered for target HR 0.746 w/n=250 pts (MOSAIC needed &gt;2200 pts for HR 0.78), heterogeneity in FOLFOXIRI duration. A power of 37% makes results hypothesis-generating at best #ASCO25 @OncoAlert @IbrahimSahinMD1 @guildsman https://t.co/RCBQfQ4G4Y
Suneel Kamath MD ● NEGATIVE DYNAMIC-III study shows no benefit of giving more chemo for ctDNA+ stage 3 colon cancer. I always say, ctDNA is amazing and cool, but it doesn't make FOLFOX (or irinotecan) more effective. #ASCO25 #CancerCare https://t.co/eYrVND47rM
Ibrahim Halil SAHIN, MD ● NEGATIVE ✳️Unpowered, non-randomized, imbalanced on MRD volume and we don’t even know clinical characteristics of triplets vs doublet regimen‼️ So many caveats in the study to conclude Irinotecan does not work ‼️ This study was not designed to test or compare doublet vs triplet ❗️A https://t.co/fyAfn5wDLv
OsmanKostekMD ● NEGATIVE #ESMO2025 | DYNAMIC-III trial ctDNA-guided adjuvant therapy in stage III colon cancer 👉 3-yr RFS: 85.3% vs 88.1% 👉 Oxaliplatin use ↓ from 88.6% → 34.8% ❗Non-inferiority not met but outcomes similar 💡 De-escalation—needs further confirmation @AnwaarSaeed3 @OncoAlert https://t.co/XgNzo2IZlU
Oriol Mirallas MD ● NEGATIVE 🚀 LAST Presidential III #ESMO25 🫴🏽 DYNAMIC-III 🩸 #ctDNA guided trial🤩 Great discussion by @GIcancerDoc ❌ NOT a positive trial for #DFS ⁉️ #OS waiting, might be positive Is #prognostic information worth the cost and burden? @OncoAlert @myESMO @ASCO @_SEOM https://t.co/WKjSHlcso5
Krishan Jethwa ● NEGATIVE 🚨DYNAMIC-III🚨 🔎R0 resected stage 3 colon cancer, post-op ctDNA + Randomized SoC vs intensified Systemic therapy ⛔️No improvement in RFS with intensification 🧐While ctDNA+ is prognostic, work is needed to identify how tx/selection may be altered to ⬆️outcomes #ASCO25 https://t.co/riIDONsprp
Dr. Cathy Eng ● NEGATIVE Dr. Tie presents Phase 2 #coloncancer and #ctDNA based on Dynamic-III for stage 3 pts for a primary endpoint of 2-RFS (goal HR &lt; .746) demonstrates if ctDNA+ 🛑 No statistical diff for dose escalation. #cancer #canceresearch #clinicaltrials https://t.co/ya5wT10rAh
Richard Dunne, MD ● NEGATIVE @jgong15 @OncoAlert @IbrahimSahinMD1 @guildsman @ASCO @GIcancerDoc @benweinbergmd @jonathan_nowak @NVijayvergiaMD @Jcj84Jeremy @aparna1024 @Ahn_Daniel_Onc @GIMedOnc @mgfakih Only 65 of 961 patients randomized saw folfoxiri. Numbers in ctDNA+ve group with escalation likely too small to make a conclusion
Yüksel Ürün ● NEGATIVE According to phase 2/3 AGITG DYNAMIC-III: Colon cancer &amp; 🧬🩸ctDNA: a warning signal. ctDNA is prognostic—not predictive for chemo escalation. Biology speaks louder than stage. Time to rethink adjuvant strategies. @ASCO @OncoAlert #ASCO25
Dr. Marwan G. Fakih ● NEGATIVE @jgong15 @OncoAlert @IbrahimSahinMD1 @guildsman @ASCO @GIcancerDoc @benweinbergmd @jonathan_nowak @NVijayvergiaMD @Jcj84Jeremy @aparna1024 @Ahn_Daniel_Onc @DrR_DUNNE @GIMedOnc I my mind this is one of the most important presentations this meeting. More of the same does not fix the problem. Not a big surprise given the lack of benefit from FOLFIRI in adj settings, including resected liver Mets