Checkpointinhibitoren beim kolorektalen Karzinom – eine neue Ära?

Abstract

Checkpoint-inhibitors have shown high response rates in some tumours such as melanomas. This article describes the data concerning the efficacy of checkpoint inhibitors in patients with colorectal cancer (CRC). Efficacy for the use of checkpoint inhibitors in CRC has only been shown for tumours with high microsatellite instability (MSI-H) or adeficient mismatch repair system (dMMR). The proportion of patients with MSI-H/dMMR cancers is 10-12% in colon cancers and 3% in rectal cancers. In cohort studies with patients that had progressed under at least one chemotherapy aresponse rate of 33% could be shown for pembrolizumab and 65% for the combination nivolumab and ipilimumab. In many patients the response was long-lasting. After 2years between 55and 75% of patients were still alive. In arandomized study comparing first-line therapy with pembrolizumab and chemotherapy progression-free survival was much longer for the pembrolizumab group (16.5 vs. 8.2months). In asmall series of patients with MSI-H/dMMR rectal cancers treatment with dostarlimab resulted in complete remission in all patients with no regrowth during an admittedly short follow-up. Aseries of patients with locally advanced MSI-H/dMMR colon cancers showed atreatment response in nearly all patients with 67% experiencing complete remission. In patients with microsatellite-stable (MSS) cancers checkpoint inhibitors showed no effect, the combination with chemotherapy at most amodest effect. Checkpoint inhibitors are the first-choice palliative treatment in patients with MSI-H/dMMR CRC and have replaced chemotherapy as the first option. Early data show ahigh response rate for the neoadjuvant treatment of MSI-H/dMMR rectal and colon cancers.