Thierry André

Combination checkpoint blockade became a first-line standard for mismatch repair-deficient metastatic colorectal cancer in 2025; the later all-lines comparison against nivolumab alone showed the CTLA-4 antibody adds to the PD-1 antibody, the first phase 3 to prove that in this disease.

The first United States approval of a HER2-directed regimen in colorectal cancer, and the basis for MOUNTAINEER-03, which is testing the combination with chemotherapy in the first line.

Every colorectal cancer should be tested for mismatch repair deficiency, because patients whose metastatic tumour is dMMR should receive pembrolizumab rather than chemotherapy as first treatment, gaining a much better chance of durable remission with fewer side effects. About a third of dMMR tumours do not respond initially, so early scans are essential and chemotherapy remains available. The trial does not apply to the 95% of metastatic colorectal cancers that are mismatch-repair proficient (the deficient share is higher in localised disease, about 15%).

The largest de-escalation exercise in adjuvant oncology, and the reason a patient with a T3 N1 colon cancer is now offered four cycles of CAPOX rather than twelve of FOLFOX, with a fraction of the neuropathy.

It gave the second PD-1 antibody a colorectal indication in mismatch repair deficient disease and, with the ipilimumab cohort that followed, set up CheckMate 8HW and the first-line combination.

FOLFOX after surgery for stage III colon cancer, still the standard 22 years later, and the reason every later adjuvant trial in this disease is an oxaliplatin trial.