111P - Positive hyperselection of sensitizing genomic alterations (GAs) in RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) patients (pts) from the phase III study of first-line FOLFIRI/cetuximab versus FOLFIRI/cetuximab followed by cetuximab (Cet) al

Background

The ERMES trial did not show non-inferiority of maintenance with Cet alone versus standard treatment. Preliminary results suggested that a strategy of de-escalation with only Cet might be effective in selected pts. Here we describe preliminary data from comprehensive genomic profiling (CGP) of CRC samples from the ERMES study.

Methods

Untreated RAS/BRAF wt mCRC pts were randomly assigned (1:1) to receive FOLFIRI/Cet until PD/toxicity (arm A) or FOLFIRI/Cet for 8 cycles followed by Cet alone (arm B). DNA from tumor tissue samples was analyzed by the Oncomine Comprehensive Assay Plus covering GAs in 500+ genes. The prognostic value of GAs was assessed in the intention-to-treat (ITT) pts’ population with available sequencing data.

Results

CGP has been successfully completed for 139 patients of the ITT population (68 in arm A and 71 in arm B). This group had a median progression free survival (mPFS) of 9.3 months (mo). The comparison of the GAs of cases within the 25^th and the 75^th mPFS percentile (34 and 36 pts, respectively), identified a signature of 34 genes altered only in the 75^th percentile cohort, thus allowing positive hyperselection of pts with good prognosis. The altered genes were associated with gene transcription and expression, SMAD 2/3/4 transcription, DNA repair, chromatin modification and Activin signalling pathways. When the signature was applied to the whole cohort of 139 pts, the hyperselection mutant (mut) pts showed longer mPFS as compared to the hyperselection wt group (16.2 vs 3.2 mo; Hazard Ratio, HR 0.1). A significant difference in mPFS was also observed in the cohort of 103 pts with mPFS <75^th percentile (12.3 mo in mut vs 3.2 mo in wt pts; HR 0.39). An exploratory analysis in the whole cohort found no significant differences in mPFS for hyperselection mut pts enrolled in arm A versus arm B (16.2 vs. 17.00 mo; HR 1.34).

Conclusions

These preliminary data suggest that CGP of RAS/BRAF wt mCRC pts receiving first-line anti-EGFR based therapy may allow hyperselection of patients with better prognosis.

Legal entity responsible for the study

The authors.

Funding

This research was financially supported Merck Serono S.p.A., Rome, Italy, an affiliate of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945).

Disclosure

All authors have declared no conflicts of interest.