Colorectal and Anal – Rapid Oral Abstract Session

The second daily highlight in GI cancer at ASCO 2025 is presented by Prof Marc Van den Eynde (Cliniques Universitaires Saint-Luc, Brussels), who has selected three particularly interesting presentations from the oral abstract session on colorectal and anal cancer.

The first study he discussed is the BREAKWATER study, a phase III trial evaluating first-line encorafenib and cetuximab plus FOLFOX in metastatic colorectal cancer. It compared this triplet therapy to standard chemotherapy (doublet/triplet ± bevacizumab) and to chemotherapy-free encorafenib + cetuximab. Results showed a clinically significant improvement in PFS: 13 months vs 7 months for standard of care. The overall response rate was 65% vs 40% in the standard chemotherapy arm. The chemotherapy-free arm (encorafenib + cetuximab) performed similarly to standard chemotherapy. Treatment-related adverse events were manageable and expected. Importantly, overall survival in the triplet arm exceeded 30 months. This represents a significant advancement for this population with poor prognoses. The regimen is poised to become a new standard of care.

The CheckMate 8HW trial is a randomised phase III study in MSI-high metastatic colorectal cancer. It compares first-line and overall therapy lines: nivolumab + ipilimumab (Nivo+IPI), nivolumab monotherapy, and standard chemotherapy. With nearly 4 years of follow-up, the Nivo+IPI arm demonstrated clear and durable benefits across all lines. Nivo+IPI also improved the composite endpoint PFS2, considering subsequent therapies. This confirms Nivo+IPI as a new standard of care in this setting. However, immune-related toxicities were higher, mainly in the first 6 months. High-grade immune toxicity may correlate with treatment benefit. Common adverse events included skin and endocrine toxicities. Starting with Nivo+IPI upfront appears more beneficial for long-term outcomes. Overall, this validates the use of Nivo-IPI in first-line metastatic colorectal cancer with MSI-high status.

There were two interesting communications about ctDNA. The first one reported on postsurgical ctDNA from the adjuvant Alliance trial (FOLFOX ± cetuximab). The trial itself was negative, but the focus was on the prognostic value of ctDNA. The test used measured tumour fraction in plasma using epigenomic profiling. It was a non-tumour-informed (tumour-agnostic) plasma-based test. Over 2,000 patients were analysed for ctDNA positivity after surgery. About 20% of patients had detectable ctDNA, linked to relapse risk. ctDNA positivity correlated with worse DFS and OS. Higher tumour fraction predicted a worse prognosis. Clearance of ctDNA was linked to improved outcomes. 

The DYNAMIC-III trial was an Australian trial investigating ctDNA-informed adjuvant therapy decisions. The test was tumour-informed, using mutations from the tumour biopsy. Two treatment strategies were compared: standard TNM-based vs ctDNA-guided escalation or de-escalation. They focused on ctDNA-positive patients in this communication. ctDNA positivity was prognostic for RFS. Clearance of ctDNA after chemotherapy was associated with a better prognosis. Escalating chemotherapy in ctDNA-positive patients did not improve 2-year RFS. The trial was underpowered and lacked standardised treatment protocols. There was also an imbalance in baseline prognostic factors. So, there is no definitive conclusion on ctDNA-driven escalation, but the prognostic value of ctDNA remains clear.