Title

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

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

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

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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