e16134 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 gastrointestinal 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) rates. Gastric and gastroesophageal data was further analyzed for pCR and MPR rate with respect to immunotherapy only versus chemoimmunotherapy regimens. 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). For gastric and gastroesophageal cancers, response rates for patients receiving immunotherapy only were comparable to those receiving chemoimmunotherapy with a PCR rate of 45.37% for IO therapy and 42.27% for chemoimmunotherapy. Conclusions: Our findings strengthen the NCCN guidelines recommending the use of neoadjuvant immunotherapy for MSI-h/dMMR localized gastrointestinal cancers. While the gastric and gastroesophageal data is insufficiently powered to draw a final conclusion, it appears to indicate that conjugate chemotherapy may not be required alongside immunotherapy. 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 esophageal, gastric, and gastroesophageal cancers - immunotherapy versus chemoimmunotherapy. Treatment for esophageal, gastric, gastroesophageal cancers Evaluable Patients pCR pCR (%) MPR MPR (%) pCR + MPR (%) Immunotherapy 108 49 45.37 17 15.74 61.11 Chemoimmunotherapy 97 41 42.27 2 2.06 44.33
Hartshorne et al. (Thu,) studied this question.