At the ESMO GI Cancers Congress 2026, Giulia Martini presented results from the CAPRI-2 GOIM trial, evaluating cetuximab-based treatment across sequential lines of therapy in molecularly selected metastatic colorectal cancer.
The presentation, titled “Cetuximab in the continuum of care of molecularly selected metastatic colorectal cancer: The CAPRI-2 GOIM trial,” was presented as abstract 2RO.
Background
Treatment sequencing remains an open question for patients with RAS and BRAF V600E wild-type metastatic colorectal cancer. In left-sided primary tumors, chemotherapy plus an anti-EGFR agent is a preferred first-line approach, but outcomes after progression are often more limited.
CAPRI-2 GOIM was designed to assess whether plasma ctDNA comprehensive genomic profiling could help identify patients who may continue to benefit from cetuximab while changing the chemotherapy backbone across later lines of treatment.
CAPRI-2 GOIM Trial Design
CAPRI-2 GOIM investigated biomarker-driven, cetuximab-based therapy across three sequential treatment lines in patients with RAS and BRAF V600E wild-type, microsatellite stable metastatic colorectal cancer. The data presented in this abstract focused on first-line FOLFIRI plus cetuximab and second-line FOLFOX plus cetuximab after first-line progression.
Plasma ctDNA comprehensive genomic profiling was performed at baseline and again at first- and second-line progression. This allowed investigators to further refine molecular selection beyond standard RAS/BRAF V600E status.
Patients without detectable pathogenic variants in genes associated with anti-EGFR resistance were defined as “negative hyperselected.” Patients with one or more such variants were classified as “positive hyperselected.” The resistance-related genes assessed included KRAS, NRAS, BRAF, PTEN, MAP2K1, NF1, FGFR, ROS1, MET, HER2, EGFR extracellular domain, PIK3CA, RET, and NTRK.
The trial is registered as NCT05312398.
Read more about CAPRI-2 GOIM Study Findings on OncoDaily.
Results
A total of 182 patients received first-line FOLFIRI plus cetuximab. Baseline plasma ctDNA profiling identified 132 patients (73%) as “negative hyperselected” and 50 patients (27%) as “positive hyperselected.”
In the first-line setting, the negative hyperselected group had higher response rates and longer progression-free survival. The objective response rate was 78.03% compared with 54.00% in the positive hyperselected group (OR 3.00; 95% CI: 1.42–6.38; p=0.00292).
Median progression-free survival was 13.8 months in negative hyperselected patients versus 9.6 months in positive hyperselected patients (HR 0.55; 95% CI: 0.39–0.78; p=0.001).
After first-line progression, 75 patients received FOLFOX plus cetuximab. In this second-line setting, the objective response rate was 27.78% in negative hyperselected cases and 20.00% in positive hyperselected cases (OR 1.53; 95% CI: 0.40–7.31; p=0.565).
Median progression-free survival remained longer in the negative hyperselected group: 8.3 months versus 4.65 months (HR 0.43; 95% CI: 0.25–0.75; p=0.003).
Median overall survival was not reached in negative hyperselected patients, compared with 22.4 months in positive hyperselected patients (HR 0.47; 95% CI: 0.30–0.73; p=0.001). When overall survival was measured from the start of second-line therapy, median OS was 27.4 months versus 15.9 months, respectively, although this difference was not statistically significant (HR 0.60; 95% CI: 0.29–1.24; p=0.170).
Conclusion
The CAPRI-2 GOIM trial suggests that plasma ctDNA comprehensive genomic profiling can identify a “negative hyperselected” subgroup of patients with RAS/BRAF V600E wild-type, microsatellite stable metastatic colorectal cancer who may derive greater benefit from cetuximab-based treatment.
In this subgroup, continuing cetuximab while switching chemotherapy from FOLFIRI to FOLFOX was associated with longer progression-free survival in the second-line setting. Overall survival from baseline was also longer in negative hyperselected patients, while overall survival measured from the start of second-line therapy was numerically longer but not statistically significant.
These findings support serial liquid biopsy profiling as a potential tool to guide anti-EGFR treatment continuation and sequencing in molecularly selected metastatic colorectal cancer.
Expert Highlights
MV Chandrakanth highlighted the CAPRI-2 GOIM data on his X page, emphasizing the role of plasma ctDNA comprehensive genomic profiling in refining anti-EGFR treatment selection across lines of therapy.
“New data from CAPRI-2 GOIM trial (ESMO GI 2026 Rapid Oral)
Plasma ctDNA CGP can help identify “negative hyperselected” RAS/BRAF WT mCRC patients who derive meaningful benefit from continuing cetuximab by simply switching the chemo backbone (FOLFIRI → FOLFOX).
Key takeaway: 73% were negative hyperselected at baseline and showed significantly better outcomes in both 1L and when continuing anti-EGFR in 2L.”
Dr Rishabh Jain also discussed the trial on his X page, framing CAPRI-2 GOIM as an example of how ctDNA hyperselection may guide whether cetuximab should be continued beyond first-line therapy.
“Should we continue cetuximab beyond first line in RAS/BRAF WT metastatic colorectal cancer?
The ESMO GI 26 CAPRI-2 GOIM trial suggests the answer may depend on ctDNA hyperselection.
Patients with:
RAS/BRAF V600E WT
MSS mCRC
No acquired resistance alterations on plasma ctDNA (“negative hyperselected”)derived substantial benefit from continuing cetuximab while switching chemotherapy.
1L: FOLFIRI + Cetuximab
ORR: 78% vs 54% (OR 3.0; P=0.003)
mPFS: 13.8 vs 9.6 months (HR 0.55)2L: FOLFOX + Cetuximab
mPFS: 8.3 vs 4.7 months (HR 0.43; P=0.003)
OS: NR vs 22.4 months (HR 0.47; P=0.001)Take-home
Instead of automatically discontinuing anti-EGFR therapy after progression, serial ctDNA profiling may identify patients who can continue benefiting from cetuximab across treatment lines.
This moves us one step closer to dynamic, biomarker-guided treatment sequencing in metastatic CRC.
Will ctDNA-guided anti-EGFR continuation become the new standard?”
More details are available in the official ESMO Gastrointestinal Cancers Congress 2026 programme.