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Published on: March 14, 2019
Baseline Liquid Biopsy in Relation to Tissue-Based Parameters in Metastatic Colorectal Cancer: Results From the
Sebastian Stintzing1,2, Susanne Klein-Scory3, Ludwig Fischer von Weikersthal4
1Department of Hematology, Oncology and Cancer Immunology (CCM), Charité-Universtätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Purpose:
The FIRE-4 study randomly assigned patients with first-line RAS wild-type (RASwt) metastatic colorectal cancer to either flourouracil (FU), folinic acid, and irinotecan (FOLFIRI) plus cetuximab until progression or intolerable toxicity (standard arm) or to FOLFIRI plus cetuximab followed by a switch maintenance treatment using FU plus bevacizumab (experimental arm). Here, we investigate the relevance of liquid biopsy (LB) RAS and BRAF testing compared with tissue-based analyses.
Patients And Methods:
LBs were taken at baseline and during treatment and were analyzed for RAS and BRAFV600E mutations using the in vitro diagnostics-certified ONCOBEAM RAS procedure (Sysmex Inostics) and digital-droplet polymerase chain reaction technology.
Results:
Six hundred seventy-two RASwt patients were randomly assigned. LBs of 540 patients were evaluable at baseline. Of those, 70 (13%) were RAS mutant (RASmut) and 38 (7%) BRAFV600E mutant. RASmut patients had significantly shorter survival compared with RASwt patients (progression-free survival [PFS], 9.0 months v 11.5 months; P < .001; hazard ratio [HR], 1.66; overall survival [OS], 22.1 months v 33.6 months; P < .001; HR, 1.85). RASmut patients had a numerically greater benefit from early switch maintenance compared with continuation of FOLFIRI/cetuximab (PFS, 10.1 months v 6.4 months; HR, 0.82; OS, 24.9 months v 16.3 months; HR, 0.57). Patients with a BRAFV600E mutation in LB showed poor outcome (PFS, 5.4 months; OS, 12.0 months). On the basis of serial LB analyses, the conversion rate from RASwt to RASmut at disease progression was significantly higher in the arm with continuous cetuximab administration than in the switch maintenance arm.
Conclusion:
LB 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 LB performed at baseline before the start of therapy.
