Oral abstract session: Cancers of the colon, rectum, and anus

The BREAKWATER study evaluated first-line treatment strategies in BRAF V600E-mutant metastatic colorectal cancer. In Cohort 3, a safety lead-in cohort, 147 patients were randomised 1:1 to receive encorafenib plus cetuximab (EC) combined with FOLFIRI vs FOLFIRI plus bevacizumab. The trial met its primary endpoint, showing a clinically meaningful and statistically significant improvement in confirmed overall response rate (65% vs 40%). Responses with EC+FOLFIRI were rapid and durable. Overall survival data were immature at the time of analysis (median follow-up ~10 months) but suggested a potential benefit. Toxicities were manageable and consistent with the known safety profiles of the individual agents, without new safety signals.

The phase III COMMIT trial investigated first-line treatment in dMMR/MSI-H metastatic colorectal cancer, comparing atezolizumab monotherapy with FOLFOX plus bevacizumab and atezolizumab. The study was initially designed as a three-arm trial, but the chemotherapy plus bevacizumab control arm was closed following the KEYNOTE-177 results, leaving the key comparison between atezolizumab alone and the triplet combination. At the pre-planned interim analysis (including 82 patients of the 102 enrolled patients), the combination arm demonstrated a progression-free survival of 24.5 months, compared with 5.3 months with atezolizumab monotherapy, with overall response rates of 86% and 46%, respectively. Despite this PFS difference, no overall survival advantage was observed. Toxicity was higher in the combination arm, with a higher number of grade 5 events reported. Besides the slow accrual and low number of patients, interpretation is further complicated by the absence of central testing for MSI/dMMR status, raising concerns regarding the true biomarker composition of the enrolled population.

The international, multi-centre, DISCO trial focused on staging of colorectal cancer patients with suspected peritoneal metastases, where accurate assessment is critical to reduce morbidity associated with futile cytoreductive surgery. Patients were randomised to either surgical staging (control arm) or diffusion-weighted MRI (DW-MRI) to estimate the peritoneal cancer index (PCI), with the primary endpoint being the proportion of futile surgical procedures. In the trial population, complete cytoreductive surgery was achieved in 80% of patients in the MRI arm vs 76% in the control arm. Open-close procedures occurred in 8% vs 11.5%, respectively. Importantly, the proportion of futile surgery was significantly reduced with MRI-based staging (27% vs 43%). Subgroup analyses suggested that this reduction was mainly driven by the Dutch cohort.

Finally, the ColoCare longitudinal cohort study evaluated associations between self-reported physical activity, cancer-related fatigue, and quality of life in >1,700 patients with newly diagnosed colorectal cancer across all disease stages. Physical activity was assessed at baseline, 6, 12 and 24 months after diagnosis and expressed as metabolic equivalent task (MET) minutes, while cancer-related fatigue and quality of life were assessed using validated EORTC questionnaires. The study reported that walking during the first year after diagnosis was consistently associated with reduced cancer-related fatigue, with the strongest effect observed in early-stage disease. In later survivorship, moderate to high levels of activity appeared to provide greater benefit. While causality cannot be established due to the observational design, the findings reinforce the clinical relevance of encouraging sustainable physical activity as part of supportive care in colorectal cancer survivorship.