OBJECTIVES: Pembrolizumab, a PD-1 inhibitor, has been approved in the US for the treatment of patients with unresectable or metastatic MSI-H/dMMR solid tumors. Given limited data on the epidemiology of MSI-H and dMMR across solid tumors (except colorectal cancer (CRC)) the current study was designed to estimate the prevalence among these cancers.

METHODS: A structured literature review identified English language publications that used immunohistochemistry for all four MMR proteins or polymerase chain replication techniques using specified NCI or Promega marker panels. Publications were selected for all tumor types except CRC using MEDLINE, EMBASE and Cochrane databases and key cancer congresses; CRC and pan-tumor genomic publications were identified through a targeted review. Meta-analysis (random effects model) was performed to estimate the pooled prevalence of MSI-H/dMMR across all solid tumors and for specific tumors. The estimates were weighted based on the overall prevalence of tumor types (based on GLOBOCAN 2012 and other databases). If sufficient data were available, prevalence was also estimated by disease stage.

RESULTS: Of 1,176 citations retrieved, 101 and 46 publications reported prevalence of MSI and dMMR and/or pMMR, respectively. Five genomic studies were included. Tumor types with large number (n) of publications, which allowed for tumor-specific meta-analyses, included gastric (n=39), ovarian (n=23), colorectal (n=20), endometrial (n=53), esophageal (n=6) and renal cancer (n=8). Overall pooled MSI-H prevalence (with 95%CI) across all tumors and stages was based on 28,213 patients and estimated at 14% (10-19%). Stage 1/2 prevalence was estimated at 15% (8-23%) while Stage 3 and Stage 4 prevalence at 9% (3-17%) and 3% (1-7%), respectively. Overall pooled dMMR prevalence across all tumor types and stages was based on 20,383 patients and estimated at 16% (11-22%).

CONCLUSIONS: This is the first comprehensive attempt to report pooled prevalence estimates of MSI-H/dMMR across solid tumors based on published data.