In an analysis reported in the Journal of Clinical Oncology, Stintzing et al found that baseline liquid biopsies identified RAS and BRAF mutations in patients with metastatic colorectal cancer considered RAS wild-type on the basis of tissue analyses.
Study Details
The study included patients from the German/Austrian FIRE-4 trial, in which patients with RAS wild-type (RASwt) metastatic colorectal cancer were randomly assigned to first-line FOLFIRI (fluorouracil [5-FU], folinic acid, and irinotecan) plus cetuximab until disease progression or intolerable toxicity or to FOLFIRI plus cetuximab followed by a switch maintenance treatment using 5-FU plus bevacizumab. Liquid biopsies were taken at baseline and during treatment and were analyzed for RAS and BRAF V600E mutations using the ONCOBEAM RAS procedure (Sysmex Inostics) and digital-droplet polymerase chain reaction technology.
Key Findings
Among 672 RASwt patients randomly assigned in the trial, liquid biopsies of 540 patients were evaluable at baseline. Of those, 70 (13%) were RAS-mutant (RASmut) and 38 (7%) were BRAF V600E–mutant.
Patients with RASmut on liquid biopsy had significantly poorer progression-free survival (median = 9.0 months vs 11.5 months, hazard ratio [HR] = 1.66, P < .001) and overall survival (median = 22.1 months vs 33.6 months, HR = 1.85, P < .001) vs RASwt patients.
RASmut patients showed a numeric progression-free survival benefit (median = 10.1 months vs 6.4 months, HR = 0.82, P = .54) and numeric overall survival benefit (median = 24.9 months vs 16.3 months, HR = 0.57, P = .10) with early switch maintenance vs continuation of FOLFIRI/cetuximab.
Patients with BRAF V600E mutation on liquid biopsy exhibited poor outcomes, with a median progression-free survival of 5.4 months and a median overall survival of 12.0 months.
The investigators concluded, “Liquid biopsy allows the detection of RAS and BRAF mutations in patients deemed RASwt on the basis of tissue analyses. These patients show outcome characteristics expected for RAS- and BRAF-mutant patients in tissue. The study thus confirms the high clinical relevance of liquid biopsy performed at baseline before the start of therapy.”
Sebastian Stintzing, MD, of Charité-Universtätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Germany, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
