Circulating tumor DNA in the blood could serve as a marker of prognosis in patients with colon cancer receiving adjuvant oxaliplatin, according to a subanalysis of the IDEA trial, presented at the European Society for Medical Oncology (ESMO) Congress 2019.1 After 2 years of adjuvant oxaliplatin-based therapy, patients with stage III colon cancer had worse 2-year disease-free survival if their blood samples before treatment contained circulating tumor DNA (ctDNA), according to Julien Taieb, MD, PhD, of Hopital European George Pompidou, Paris.
The independent prognostic value of ctDNA is confirmed for the first time in patients coming from a phase III trial [in colon cancer].— Julien Taieb, MD, PhD
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“The independent prognostic value of ctDNA is confirmed for the first time in patients coming from a phase III trial [in colon cancer],” he noted.
The patients were enrolled in the IDEA-France trial, which investigated 3 vs 6 months of oxaliplatin-based adjuvant chemotherapy for patients with stage III colon cancer. Although both ctDNA-positive and ctDNA-negative patients responded more favorably to 6 months of adjuvant oxaliplatin than 3 months, “3 months of treatment seems to be associated with a particularly poor outcome in ctDNA-positive patients,” added Dr. Taieb.
The aim of the current analysis was to determine the prognostic and predictive value of ctDNA in treatment. The investigators identified ctDNA using two methylated markers—WIF1 and NPY—by digital droplet polymerase chain reaction. Comparisons regarding tumor characteristics and disease-free survival were done between patients with ctDNA-positive and ctDNA-negative samples in the 6- and 3-month treatment arms.
A total of 805 patients had blood samples analyzed for ctDNA prior to starting chemotherapy. Of these patients, 696 (86.5%) were ctDNA-negative and 109 (13.5%) were ctDNA-positive. Those with ctDNA-positive samples were found to have more advanced tumors, as determined by such characteristics as stage T4, poor differentiation, and tumor perforation.
The 2-year disease-free survival rate was 64% for patients with ctDNA-positive samples vs 82% for patients with ctDNA-negative samples (hazard ratio [HR] = 1.75; P = .001). Multivariate analysis confirmed the presence of ctDNA as an independent prognostic marker (adjusted HR = 1.85; P < .001). “This was observed in both patients with high-risk (T4, N2, or both) or low-risk stage III disease (P < .0001), although it was not significant anymore in the low-risk (T–-3/N1) patients (P < .07),” Dr. Taieb added. Adjuvant oxaliplatin treatment for 6 months produced better outcomes than such treatment for 3 months, both in patients with ctDNA-negative samples (HR = 0.69; P = .015) and in those with ctDNA-positive samples (HR = 0.50; P = .033).
In the main analysis of the IDEA-France trial, the 3-year disease-free survival was 75.7% for patients receiving 6 months of treatment and 72.1% with the 3-month regimen—a 3.6% difference favoring longer treatment (P = .011).2
Dr. Taieb acknowledged some limitations of the study: 200 additional samples remain to be analyzed, investigators employed a sampling approach that is not optimal, the analysis was post hoc, and data for patients receiving CAPOX (capecitabine/oxaliplatin) were limited. “Confirmation of these results in another IDEA study will be valuable,” he added.
Jordan D. Berlin, MD, Ingram Professor of Clinical Research at Vanderbilt University Medical Center, Nashville, commented that the ctDNA study was “interesting and important, broadening our knowledge on the use of ctDNA in personalizing our adjuvant therapy choices.”
It is possible in the future that ctDNA will be shown to be a tool that helps us decide on the use of and/or duration of adjuvant therapy in colorectal cancer.— Jordan D. Berlin, MD
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Although he noted that confirmatory data are needed, “It is possible in the future that ctDNA will be shown to be a tool that helps us decide on the use of and/or duration of adjuvant therapy in colorectal cancer,” Dr. Berlin commented. “These data are important steps in moving us in that direction.” ■
DISCLOSURE: Dr. Taieb has received honoraria from or served as an advisor for Roche, Merck, Amgen, Celgene, MSD, Servier, Sanofi, Lilly, Cirtex, and Pierre Fabre. Dr. Berlin reported financial relationships with numerous companies, but none relevant to this study.
1. Taieb J, Taly V, Vernerey D, et al: Analysis of circulating tumor DNA from patients enrolled in the IDEA-France phase III trial: Prognostic and predictive value for adjuvant treatment duration. ESMO Congress 2019. Abstract LBA30_PR. Presented September 28, 2019.
2. André T, Vernerey D, Mineur L, et al: Three versus 6 months of oxaliplatin-based adjuvant chemotherapy for patients with stage III colon cancer: Disease-free survival results from a randomized, open-label, international duration evaluation of adjuvant (IDEA) France, phase III trial. J Clin Oncol 36:1469-1477, 2018.