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

Author(s): Jeanne Tie, M.D., Joshua D. Cohen, M.Phil., Kamel Lahouel, Ph.D., Serigne N. Lo, Ph.D., Yuxuan Wang, M.D., Ph.D., Suzanne Kosmider, M.B., B.S., Rachel Wong, M.B., B.S., Jeremy Shapiro, M.B., B.S., Margaret Lee, M.B., B.S., Sam Harris, M.B., B.S., Adnan Khattak, M.B., B.S., Matthew Burge, M.B., B.S., et al., for the DYNAMIC Investigators*

Source: N Engl J Med 2022; 386:2261-2272 DOI: 10.1056/NEJMoa2200075

Excellent study demonstrating the value of evaluation of ctDNA/molecular disease and impact of adjuvant chemotherapy. Guidelines will change rather significantly (for different cancers) in this decade, as to who actually needs post-operative chemotherapy. More prolonged follow-up is warranted.

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. opens in new tab.)

Author Affiliations

From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of Medicine, Dentistry, and Health Sciences, University of Melbourne (J.T., P.G.), the Department of Medical Oncology, Eastern Health (R.W., M.L.), the Eastern Health Clinical School, Faculty of Medicine, Nursing, and Health Sciences, Monash University (R.W., M.L.), the Department of Medical Oncology, Cabrini Health (J.S.), the Department of Medical Oncology, Monash Health (M.H.), the Department of Medical Oncology, St. Vincent’s Hospital (S.-A.M.), and the Department of Medical Oncology, Northern Health (B.L.), Melbourne, VIC, the Research and Biostatistics Group, Melanoma Institute Australia, and the Faculty of Medicine and Health, University of Sydney, Sydney (S.N.L.), the Department of Medical Oncology, Bendigo Health, Bendigo, VIC (S.H.), the Department of Medical Oncology, Fiona Stanley Hospital, and Edith Cowan University, Perth, WA (A.K.), the Department of Medical Oncology, Royal Brisbane and Women’s Hospital, and the University of Queensland, Brisbane, QLD (M.B.), Newcastle Private Hospital (J.L.), and the Department of Medical Oncology, Calvary Mater Newcastle Hospital (F.D.), Newcastle, NSW, the Department of Medical Oncology, Royal Hobart Hospital, Hobart, TAS (L.N.), and South West Healthcare, Warrnambool, VIC (T.H.) — all in Australia; the Ludwig Center for Cancer Genetics and Therapeutics (J.D.C., Y.W., J.P., N.S., L.D., M.P., N.P., K.W.K., B.V.), the Division of Biostatistics and Bioinformatics (K.L., C.T.), Department of Oncology, Sidney Kimmel Comprehensive Cancer Center (J.D.C., Y.W., J.P., N.S., L.D., M.P., R.H., A.M.L., N.P., K.W.K., B.V.), the Sol Goldman Pancreatic Cancer Research Center (J.D.C., Y.W., J.P., N.S., L.D., M.P., R.H., A.M.L., N.P., K.W.K., B.V.), and the Departments of Pathology (R.H.) and Medicine (A.M.L.), Johns Hopkins University School of Medicine, the Howard Hughes Medical Institute (J.P., N.S., B.V.), the Department of Biomedical Engineering, Johns Hopkins University (J.D.C.), and the Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health (C.T.) — all in Baltimore; and the Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia (S.N.L.).

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