Colorectal Cancer

In this video, Dr Gertjan Rasschaert, consultant GI oncology at the University Hospitals Leuven summarises the key take home messages from ASCO GI 2025 related to colorectal cancer (CRC). 

Arguably the most important presentation in CRC featured the results of the CheckMate 8HW study evaluating dual immunotherapy with nivolumab and ipilimumab (nivo-ipi) in patients with microsatellite-high (MSI-H) metastatic CRC (mCRC).¹ These long-awaited results demonstrated a significantly better progression-free survival (PFS) with nivo-ipi compared to nivo alone, with a hazard ratio (HR) of 0.62 (95%CI: 0.48-0.81). At three years, this translated into a PFS rate of 68% for nivo-ipi as compared to 51% for nivo alone, establishing the nivo-ipi combination as a potential new standard of care for these patients.¹

Also in the oral abstract session on CRC, Prof Scott Kopetz (MD Anderson Cancer Center, Houston) shared the first results of the randomised phase III BREAKWATER trial.² This study revealed that the combination of mFOLFOX6 with encorafenib and cetuximab led to a significantly better objective response rate (ORR) than standard of care first line therapy in patients with BRAF^V600E-mutant mCRC (60.9% vs. 40.0%; OR[95%CI]: 2.44[1.403- 4.253]).² These findings were convincing enough for the FDA to grant this treatment an accelerated approval in this setting.

ASCO GI 2025 also featured the final results of the BESPOKE trial, a study evaluating the potential of a tumor-informed circulating tumor (ct)DNA assay in patients with stage II/III CRC. Interestingly. These results showed that adjuvant chemotherapy only provided a clinical benefit in patients with MRD positivity as assessed on ctDNA. Furthermore, ctDNA clearance at 3 and 6 months proved to be significantly associated with disease-free survival. Not surprisingly, during the surveillance phase, ctDNA MRD status was significantly associated with recurrence.³ While these findings illustrate the potential of ctDNA in this setting, Dr Rasschaert continues to be somewhat skeptical on the readiness of this technology for clinical practice. The main reasons for this skepticism are a lack of randomised data, the high cost and heterogeneity of the existing ctDNA assays and the relatively short follow-up in this study (~2 years). Therefore, he concludes that it will probably take a bit more time before ctDNA-based treatment decisions will become a reality in the routine care for CRC patients.

ALASCCA is a large (~600 patients), randomised controlled trial evaluating the effect of prophylactic aspirin in patients with stage II/III CRC harboring a mutation in the PIK3CA pathway.⁴ While previous studies evaluating prophylactic aspirin in CRC were negative, this trial turned out to be positive. At three years, the cumulative rate of CRC recurrence was reported at 7.7% in the aspirin arm as compared to 14.1-16.8% in the placebo arm (depending on the type of PIK3CA mutation).⁴ This 50% reduced risk of recurrence is a striking finding and will probably prove to be practice changing.

During the rapid oral session on CRC, Fakih et al. presented the results of a phase II study evaluating different doses of botensilimab (an Fc enhanced anti-CTLA4 agent), with or without balstilimab (anti-PD1) in patients with chemotherapy refractory, mismatch-repair proficient (pMMR) mCRC. With the botensilimab (75 mg q6w) -balstilimab (150 mg 2qw) combination, an ORR of 19% was obtained.⁵ This is a promising finding, given the fact that traditional immune checkpoint inhibition in pMMR CRC patients only yielded an ORR of 1-2%. Additional promising results with the botensilimab-balstilimab combination were obtained in two (small) neoadjuvant studies indicating a pathological complete response rate of 30-40% in patients with microsatellite stable (MSS)/pMMR CRC.^6,7 For Dr Rasschaert, these findings provide further support for a planned clinical trial in Belgium that will assess the potential of neoadjuvant dostarlimab in patients with MSS/pMMR stage II/III CRC.