34P - Circulating tumor DNA (ctDNA) testing in tissue RAS/BRAF wild-type metastatic colorectal carcinoma (mCRC) patients (pts) enrolled in the LIquid BIopsy monoclonal Antibodies (LIBImAb) study

Background

Tissue RAS/BRAF testing is the golden standard for mCRC pts candidate to treatment with anti-EGFR monoclonal antibodies. RAS/BRAF mutations have been detected in ctDNA from up to 10% treatment-naive mCRC pts RAS/BRAF wild-type (RAS/BRAF^WT) on tissue, while approximately 30% of RAS/BRAF^WT pts treated with anti-EGFR agents show RAS/BRAF mutations in ctDNA at progression.

Methods

LIBImAb is a phase III, randomized, open-label, comparative, multi-centre trial to assess the superiority of bevacizumab versus cetuximab in combination with FOLFIRI in mCRC pts, RAS/BRAF^WT on tumor tissue and RAS/BRAF mutant (RAS/BRAF^mut) at liquid biopsy. This trial is supported by the Italian Drug Agency (AIFA). Blood samples from enrolled pts are collected and shipped to a centralized laboratory. Plasma is analyzed by the Idylla® ctKRAS-ctNRAS/BRAF mutation assays (Biocartis). Pts RAS/BRAF^mut on ctDNA at baseline are randomized to receive FOLFIRI/cetuximab or FOLFIRI/Bevacizumab. Pts RAS/BRAF^WT on baseline plasma test, are treated with FOLFIRI/cetuximab up to 8 cycles and, if not progressed, they are retested for RAS/BRAF mutations on ctDNA. RAS/BRAF^mut pts at re-screening are randomized to continue cetuximab or to switch to bevacizumab.

Results

As of March 15 2024, 318 tissue RAS/BRAF^WT mCRC pts at baseline and 178 pts at re-screening were tested. The median turnaround time (TAT) from blood sampling to results was 48 hours (range 24-96). Baseline plasma testing detected RAS mutations in 24/318 pts (7.5%). Fifteen pts carried variants in KRAS (4.7%), 6 in NRAS (1.9%) and 3 in BRAF^V600 (0.9%), defining an overall concordance rate of 92.4% with tissue. For the 178 samples at re-screening, the rate of RAS/BRAF^mut cases was 8.5%. In particular, 11 KRAS (6.2%), 3 NRAS (1.7%), and 1 BRAF^V600 (0.6%)variants were found.

Conclusions

These data show the feasibility of ctDNA-based prospective enrolment in an interventional trial using a test with a rapid TAT for screening RAS/BRAF status in plasma. Our preliminary findings also suggest that ctDNA testing can better recapitulate tumor heterogeneity providing complementary information to tissue genomic profiling.

Legal entity responsible for the study

The authors.

Funding

Italian Drug Agency (AIFA).

Disclosure

All authors have declared no conflicts of interest.