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PLCRC-ORCA: Liquid biOpsies in Ras wildtype non-liver limited metastasized colorectal CAncer patients: an exploratory study.

One of the treatment options for patients with metastatic colorectal cancer (mCRC) is an EGFR blocker. It is known that patients with a mutation in one of the RAS genes do not benefit from the treatment with an EGFR blocker. About 50% of patients with mCRC have a mutation in RAS. In addition to primary resistance, RAS mutations encourage induced resistance to anti-EGFR therapy. Apart from repeated biopsies, no other methods are currently available to track molecular changes during anti-EGFR treatment.

Circulating tumor DNA
In patients with cancer, small fragments of DNA from the tumor are continuously released into the blood; this is called circulating tumor DNA (ctDNA). New techniques can be used to detect ctDNA in the blood in almost any CRC patient. Since blood collection is relatively non-invasive, the analysis of ctDNA can be applied several times to verify the presence of mutations. This allows tracking the development of resistance during the anti-EGFR therapy for CRC.

PLCRC-ORCA was set up to investigate the onset of mutations in the RAS genes and in other genes during systemic treatment in mCRC. In addition, the clinical progress of the disease is followed, as well as the occurrence of resistance to therapy.

Primary objective ORCA
Research on the RAS mutation status in patients with RAS-wildtype mCRC over time, correlated to (the effect of) treatment.

Study design
PLCRC-ORCA is an observational study. 100 patients included in PLCRC who have given permission for blood collection and will be treated in the first line with either FOLFIRI-cetuximab or CAPOX-bevacizumab can participate in this substudy.
Before the start of treatment and approximately every 8 weeks after that, additional blood will be taken to analyse ctDNA in the plasma and to determine the RAS mutation status. The last blood sample is collected after the last systemic treatment.

Conclusion
The ctDNA of 100 patients with RASwt mCRC will be collected and analyzed every 8 weeks with the aim of tracking the RAS mutation status during systemic treatment and investigating the relationship with therapy resistance.

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