How I treat MSI cancers with advanced disease

Abstract

Mismatch repair deficiency (dMMR) results in microsatellite instability (MSI) and is strongly associated with responsiveness to programmed death-1 receptor (PD-1)-blocking antibodies. Probably the main driver for the observed high efficacy of immune checkpoint inhibitors in dMMR tumours is the remarkably high tumour mutational burden. MSI can be detected using immunohistochemistry and/or PCR. In addition, next-generation sequencing is becoming increasingly available to clinical laboratories as a cost-effective and scalable method to evaluate multiple genetic aberrations including MSI. Efficacy of PD-1-blockade in MSI tumours is similar for patients with colorectal cancer (CRC; objective response rate (ORR) 36%) or a different cancer type (ORR 46% across 14 other cancer types). Based on these results, PD-1-blocking antibody pembrolizumab was the first tumour-agnostic treatment to be granted Food and Drug Administration approval based on the presence of MSI as a biomarker. Currently, there is no approved PD-1-blocking antibody for MSI cancers in Europe. Here, we present our experience with the screening for MSI and the treatment of patients with advanced disease of MSI CRC and non-CRC with immunotherapy.