In contrast to other tumour types inhibitors of PD-1/-L1 or CTLA 4 have not yet shown relevant efficacy in unselected colorectal cancer. Based on the high mutational burden, deficient mismatch repair (dMMR) or microsatellite instable (MSI-H) tumours are yet the only subgroup, which is amenable to checkpoint inhibition. These tumours show relevant and durable responses in the refractory setting by PD-1/-L1 +/- CTLA 4 inhibition. Thus, ongoing phase 3 trials in this subgroup evaluate immunotherapy in the adjuvant setting as well as in the first line metastatic setting with or without chemotherapy. For the by far larger subgroup of non-dMMR/MSI-H patients (95% in the metastatic setting) combination regimen are urgently required, either with chemotherapy and/or molecular targeting drugs, local ablative treatments or other immunotherapeutic agents (e.g. CEA-TCB).
