Role of immune checkpoint inhibitors in the treatment of colorectal cancer: focus on nivolumab.

Introduction: Metastatic colorectal cancer (mCRC) is a challenging disease, whose systemic therapy has traditionally been based on a generalized population of patients, with unsatisfactory clinical outcomes. Immunotherapy has been shown to be efficacious in hypermutated tumors, such as those with microsatellite-instability (MSI-H). Nivolumab, and other immune checkpoint inhibitors (ICI), have recently been evaluated in MSI-H mCRC, with remarkable results.Areas covered: Focused on nivolumab, we aim to present the rationale for the applicability of ICI in MSI-H CRC, and the results of completed phase I/II studies. Ongoing studies, including randomized clinical trials, and perspectives of immunotherapy in clinical scenarios in CRC will be discussed.Expert opinion: Phase I and II clinical trials provide strong evidence for the use of nivolumab and other ICI in the systemic therapy of MSI-H mCRC. Regulatory approvals are restricted to subsequent lines of therapy, but preliminary results in treatment-naïve patients are encouraging. The findings for advanced disease and in the pilot phase II study in early-stage colon cancer open a new avenue for the applicability of immunotherapy in neoadjuvant and adjuvant settings, which are currently under investigation. With the exception of POLE-mutated patients, there is little evidence for the use of immunotherapy in MSS patients.