Structured literature review (SLR) and meta-analyses of the prevalence of microsatellite instability high (MSI-H) and deficient mismatch repair (dMMR) in gastric, colorectal, and esophageal cancers.

Abstract

e15074 Background: Pembrolizumab is approved in the US for treatment of unresectable/metastatic MSI-H/dMMR solid tumors progressing after standard prior treatment. While some data exist on MSI-H/dMMR prevalence in colorectal cancer (CRC), data on other gastrointestinal (GI) cancers is sparse. Methods: An SLR covering solid tumor types identified English language publications using immunohistochemistry (IHC) for all 4 MMR proteins or polymerase chain reaction (PCR) techniques using specified NCI or Promega marker panels. A targeted review was conducted for CRC due to larger volume of publications in this tumor type. MEDLINE, EMBASE, Cochrane databases and key cancer congresses were searched for relevant articles. Among eligible studies, meta-analyses were performed (random effects model) on the prevalence of MSI-H and dMMR among gastric, colorectal and esophageal cancers. If possible, prevalence estimates were also obtained by geography, disease stage, and histology. Results: Of 1,176 citations retrieved in the full review, 35, 17 and 6 studies reported prevalence of MSI-H and/or dMMR in gastric, CRC, and esophageal cancers, respectively. Among gastric cancers, MSI-H pooled prevalence (with 95% CI) from 32 studies (16,308 patients) was estimated at 11% (9-12%) and dMMR pooled prevalence from 4 studies (854 patients) was estimated at 8% (2-17%); in stage 4 cancers, the prevalence was 7% (4-9%; 10 studies; 383 patients). In CRC, MSI-H pooled prevalence from 14 studies (8,156 patients) was estimated at 13% (10-16%) and dMMR pooled prevalence from 4 studies (11,434 patients) was estimated at 10% (5-15%). For stage 4 CRC, the prevalence was 5% (1-10%; 4 studies; 252 patients). Among esophageal cancers, MSI-H pooled prevalence from 6 studies (731 patients) was estimated at 4% (0-11%). Conclusions: This comprehensive SLR provides prevalence estimates of MSI-H and dMMR across 3 key GI tumors based on published data. The prevalence estimates of MSI-H among gastric cancer and CRC were similar to their corresponding dMMR prevalence estimates. MSI-H prevalence appeared to be lower for advanced stage gastric cancer and CRC.