Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer

Tie, J; Cohen, JD; Lahouel, K; Lo, SN; Wang, Y; Kosmider, S; Wong, R; Shapiro, J; Lee, M; Harris, S; Khattak, A; Burge, M; Harris, M; Lynam, J; Nott, L; Day, F; Hayes, T; McLachlan, SA; Lee, B; Ptak, J; Silliman, N; Dobbyn, L; Popoli, M; Hruban, R; Lennon, AM; Papadopoulos, N; Kinzler, KW; Vogelstein, B; Tomasetti, C; Gibbs, P; DYNAMIC Investigators

Author(s): Tie, J; Cohen, JD; Lahouel, K; Lo, SN; Wang, Y; Kosmider, S; Wong, R; Shapiro, J; Lee, M; Harris, S; Khattak, A; Burge, M; Harris, M; Lynam, J; Nott, L; Day, F; Hayes, T; McLachlan, SA; Lee, B; Ptak, J; Silliman, N; Dobbyn, L; Popoli, M; Hruban, R; Lennon, AM; Papadopoulos, N; Kinzler, KW; Vogelstein, B; Tomasetti, C; Gibbs, P; DYNAMIC Investigators;
Details: Publication Year 2022-06-16,Volume 386,Issue #24,Page 2261-2272
Journal Title: New England Journal of Medicine
Publication Type: Research article
Abstract: BACKGROUND: The role of adjuvant chemotherapy in stage II colon cancer continues to be debated. The presence of circulating tumor DNA (ctDNA) after surgery predicts very poor recurrence-free survival, whereas its absence predicts a low risk of recurrence. The benefit of adjuvant chemotherapy for ctDNA-positive patients is not well understood. METHODS: We conducted a trial to assess whether a ctDNA-guided approach could reduce the use of adjuvant chemotherapy without compromising recurrence risk. Patients with stage II colon cancer were randomly assigned in a 2:1 ratio to have treatment decisions guided by either ctDNA results or standard clinicopathological features. For ctDNA-guided management, a ctDNA-positive result at 4 or 7 weeks after surgery prompted oxaliplatin-based or fluoropyrimidine chemotherapy. Patients who were ctDNA-negative were not treated. The primary efficacy end point was recurrence-free survival at 2 years. A key secondary end point was adjuvant chemotherapy use. RESULTS: Of the 455 patients who underwent randomization, 302 were assigned to ctDNA-guided management and 153 to standard management. The median follow-up was 37 months. A lower percentage of patients in the ctDNA-guided group than in the standard-management group received adjuvant chemotherapy (15% vs. 28%; relative risk, 1.82; 95% confidence interval [CI], 1.25 to 2.65). In the evaluation of 2-year recurrence-free survival, ctDNA-guided management was noninferior to standard management (93.5% and 92.4%, respectively; absolute difference, 1.1 percentage points; 95% CI, -4.1 to 6.2 [noninferiority margin, -8.5 percentage points]). Three-year recurrence-free survival was 86.4% among ctDNA-positive patients who received adjuvant chemotherapy and 92.5% among ctDNA-negative patients who did not. CONCLUSIONS: A ctDNA-guided approach to the treatment of stage II colon cancer reduced adjuvant chemotherapy use without compromising recurrence-free survival. (Supported by the Australian National Health and Medical Research Council and others; DYNAMIC Australian New Zealand Clinical Trials Registry number, ACTRN12615000381583.).
Keywords: *Antineoplastic Agents/therapeutic use; Antineoplastic Combined Chemotherapy Protocols/therapeutic use; Australia; *Chemotherapy, Adjuvant/methods; *Circulating Tumor DNA/analysis/blood; *Colonic Neoplasms/blood/mortality/pathology/therapy; Disease-Free Survival; Fluorouracil/therapeutic use; Humans; Neoplasm Recurrence, Local/prevention & control; Neoplasm Staging; Oxaliplatin/therapeutic use
Department(s): Medical Oncology
PubMed ID: 35657320
Publisher's Version: https://doi.org/10.1056/NEJMoa2200075
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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