Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer
Document Type
Journal Article
Publication Title
New England Journal of Medicine
Volume
386
Issue
24
First Page
2261
Last Page
2272
PubMed ID
35657320
Publisher
Massachusetts Medical Society
School
School of Medical and Health Sciences
RAS ID
52674
Funders
Australian National Health and Medical Research Council, grant (APP1085531)
Medical Research Future Fund, grant (APP1194970)
Marcus Foundation Virginia and D.K. Ludwig Fund for Cancer Research
Lustgarten Foundation
Conrad R. Hilton Foundation
Sol Goldman Charitable Trust John Templeton Foundation
National Institutes of Health, grants (CA62924, CA009071, GM136577, and CA06973)
Eastern Health Research Foundation, Linda Williams Memorial Grant
Grant Number
NHMRC Number : APP1085531
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.
DOI
10.1056/NEJMoa2200075
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Comments
Tie, J., Cohen, J. D., Lahouel, K., Lo, S. N., Wang, Y., Kosmider, S., ... & Gibbs, P. (2022). Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer. New England Journal of Medicine, 386, p. 2261-2272.
https://doi.org/10.1056/NEJMoa2200075