[Checkpoint inhibitors in colorectal carcinoma: are we entering a new era?]

Abstract

Background: Checkpoint-inhibitors have shown high response rates in some tumours such as melanomas.

Objectives: This article describes the data concerning the efficacy of checkpoint inhibitors in patients with colorectal cancer (CRC).

Current data: Efficacy for the use of checkpoint inhibitors in CRC has only been shown for tumours with high microsatellite instability (MSI-H) or a deficient 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 a response 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 2 years between 55 and 75% of patients were still alive. In a randomized study comparing first-line therapy with pembrolizumab and chemotherapy progression-free survival was much longer for the pembrolizumab group (16.5 vs. 8.2 months). In a small 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. A series of patients with locally advanced MSI-H/dMMR colon cancers showed a treatment 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 a modest effect.

Conclusions: 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 a high response rate for the neoadjuvant treatment of MSI-H/dMMR rectal and colon cancers.

Keywords: Colonic neoplasms; Microsatellite instability; Neoadjuvant therapy; Palliative care; Rectal neoplasms.