Liquid biopsy identifies relapse in patients with colorectal cancer after surgery

In a landmark trial, Prof. Julien Taieb (Hopital European Georges Pompidou, France) presented the phase 3 IDEA-FRANCE trial, in which 805 stage 3 colorectal cancer (CRC) patients were prospectively enrolled to have a liquid biopsy 4 weeks post-surgery and prior to adjuvant chemotherapy. Of these patients, 109 (13.5%) had circulating tumour DNA (ctDNA) in their blood. In this group, 2-year disease-free survival (DFS) was 64%, compared with 82% in those who were ctDNA-negative [1]. The study not only confirmed ctDNA to be an important independent prognostic marker. Although not designed nor powered to provide clear predictive evidence (patients where not randomised to receive either 3 or 6 months of treatment according to their ctDNA status), patients with ctDNA fared significantly worse when treated with 3 months chemotherapy as compared to 6 months.

A substantial number (30-50%) of patients with localised CRC relapse, despite primary optimal therapy. This study aimed to analyse the role of liquid biopsy in identifying patients with CRC who are likely to relapse after surgery. "In this large prospective trial, we confirmed that ctDNA is an independent prognostic factor in colorectal cancer and that approximately 6 out of 10 patients who are ctDNA-positive will remain disease-free 2 years after standard adjuvant chemotherapy, compared with 8 out of 10 of those who are ctDNA-negative," said Prof. Taieb.

IDEA-FRANCE also showed that 6 months of adjuvant treatment was superior to 3 months in both ctDNA-positive and -negative patients (see Figure). Furthermore, ctDNA-positive patients treated for 6 months had a similar prognosis to ctDNA-negative patients treated for 3 months. Adjuvant therapy was FOLFOX (folinic acid, fluorouracil, and oxaliplatin) in 90% of cases.

Figure. ctDNA and treatment arm



© Julien Taieb (provided by ESMO).

"ctDNA testing did not predict which patients should have 3 or 6 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 CRC," said Prof. Taieb. "In all subgroups, ctDNA-positive patients who only had 3 months of adjuvant therapy had the worst prognosis," he added.

1. Taieb J et al. ESMO Congress 2019. Abstract LBA30_PR.

Posted on 26 November, 201928 March, 2024