Response rate of MSI-high/dMMR upper and lower GI cancers to neoadjuvant immunotherapy: A systematic review.

403 Background: The success of immunotherapy to treat metastatic microsatellite instability high (MSI-h)/deficient mismatch repair (dMMR) cancers has generated interest for potential use in the neoadjuvant setting. The National Comprehensive Cancer Network (NCCN) Guidelines for MSI-h gastric, gastroesophageal, and rectal cancer recommend considering neoadjuvant immunotherapy in the localized setting, but the recommendation is based on small phase II trials with only a few dozen patients. Despite promising initial results, evidence to support this practice remains limited. Methods: To strengthen the case for using neoadjuvant immunotherapy to treat localized gastric, gastroesophageal, and rectal cancers, we conducted a systematic review to identify patients who received neoadjuvant immunotherapy for localized MSI-H/dMMR gastric, gastroesophageal, colon, and rectal cancers to determine the overall pathologic complete response (pCR) and major pathologic response (MPR, defined as at least 90% tumor shrinkage) rate following neoadjuvant immunotherapy. PubMed search parameters included microsatellite instability high (MSI-high) OR Mismatch repair deficient (dMMR) AND neoadjuvant immunotherapy. Case reports were excluded. Results: Review of the MSI-h/dMMR gastric and gastroesophageal populations included 264 patients from 18 studies, with a pCR (45.42%) and 28 with 90-99% tumor shrinkage for a MPR 55.28%. In the colon and rectal cancer populations, 701 patients across 18 studies showed pCR 70.19% and MPR 79.74% (68.91% and 83.58% for colon, respectively, and 89.36% and 94.68% for rectal). Conclusions: Our findings strengthen the NCCN guidelines recommending the use of neoadjuvant immunotherapy for MSI-h/dMMR localized gastrointestinal cancers. Further research should seek to determine the optimal immunotherapy regimen, including duration, and evaluate the potential for nonoperative management in patients who have a complete clinical response to treatment. Rate of pCR/MPR in MSI-high/dMMR gastric, gastroesophageal, colorectal cancers. Number of patients Number of studies pCR (%) MPR (%) Gastric and gastroesophageal cancers 264 18 45.42 55.28 Colorectal cancers 701 18 70.19 79.74