September 28, 2019 -- A blood test showed potential for predicting relapse in nonmetastatic colon cancer patients and for reducing unnecessary treatments in a large study reported in a late-breaking presentation on September 28 at the European Society for Medical Oncology (ESMO) Congress in Barcelona, Spain.
The prospective, phase III study -- International Duration Evaluation of Adjuvant Chemotherapy - France (IDEA-France) -- included 805 patients with stage III colon cancer. Among the patients, 13.5% had circulating tumor DNA (ctDNA) in their blood after resection and prior to treatment with chemotherapy. The disease-free survival rate was much lower for those with ctDNA than for those without, at 64% versus 82%, reported Dr. Julien Taieb, PhD, head of gastroenterology and digestive oncology at the Hôpital Européen Georges-Pompidou in Paris, and colleagues.
In a statement from ESMO, Taieb said the study confirms ctDNA as an independent prognostic biomarker in colorectal cancer.
IDEAs on duration of chemo
The study was part of a multinational project organized by the IDEA collaboration comparing three months of oxaliplatin-based chemotherapy to a standard six-month treatment course in randomized trials of patients with stage II/III colon cancer. The goal was to see if patients could get the benefits of adjuvant chemotherapy but with a shorter and therefore less toxic treatment course. Two types of oxaliplatin-based chemotherapy regimens were tested: capecitabine and oxaliplatin, known as CAPOX, and fluorouracil, leucovorin, and oxaliplatin, known as FOLFOX.
In 2018, an analysis of pooled studies for almost 13,000 patients showed that disease-free survival was superior with the standard six months of treatment (Grothy et al, New England Journal of Medicine, March 29, 2018, Vol. 378, pp. 1177-1188).
Looking at subsets, among those who received CAPOX, three months sufficed; however, for FOLFOX, six months of treatment was better. In an exploratory analysis of both regimens combined, those with lower-risk cancers had similar disease-free survival rates, regardless of whether they were treated for three or six months.
Dr. Richard Schilsky, chief medical officer of the American Society of Clinical Oncology, concluded at the time that three months of CAPOX might be appropriate for some patients, and he called for better biomarkers to predict risk and response, as well as less-toxic, effective treatments (NEJM, March 29, 2018, Vol. 378, pp. 1242-1244).
In the IDEA-FRANCE data presented at ESMO 2019, most of the patients (90%) in the analysis were treated with FOLFOX. Patients had a similar prognosis whether they were treated for three months or six months, regardless of whether they were positive or negative for ctDNA after surgery and prior to chemotherapy, the researchers reported.
"ctDNA testing did not predict which patients should have three or six months of adjuvant chemotherapy and there is continuing debate over the optimal type and duration of treatment for patients who are ctDNA positive, but we do now know that ctDNA is a major prognostic factor which will be very useful in stratifying patients and driving future trials of colorectal cancer," Taieb said in the ESMO statement. "In all subgroups, [ctDNA-positive] patients who only had three months of adjuvant therapy had the worst prognosis."
The IDEA-FRANCE study is one of the first to show that liquid biopsy may help identify which patients with early-stage colon cancer are clear after surgery and do not need chemotherapy, though more research is needed to confirm this finding, Alberto Bardelli, PhD, of the University of Turin in Italy, said in the statement.