Background: Immunotherapy (IO) has shown remarkable efficacy in gastrointestinal (GI) cancers with high microsatellite instability (MSI-H). We evaluated real world outcomes of patients treated with neoadjuvant IO for MSI-H colorectal (CRC) and gastroesophageal (GE) cancers. Methods: We queried diagnoses, pathology reports, and clinic notes of patients receiving IO at Massachusetts General Hospital from October 2014 to March 2022 using the Research Patient Data Registry and MATLAB. 1140 patients were identified with esophageal, gastric, colon, or rectal primaries. Of these, 56 were MSI-H and seven received neoadjuvant IO with curative intent. Results: Of the seven patients who received neoadjuvant IO for MSI-H CRC or GE cancers, three patients achieved complete pathologic response (pCR). Three patients had partial responses; one had a single residual lymph node tumor cell, one had residual T1b tumor and negative nodes, and one had residual T3 tumor and positive nodes. All patients with pCR had non-metastatic disease. Three of four patients with partial responses or progression had metastatic disease. Five patients had no recurrence by median follow-up of 10 months post-resection. One patient's cancer recurred 15 months post-resection, and one patient had progressive disease on neoadjuvant IO so did not undergo primary resection. Conclusions: Neoadjuvant IO shows promise for MSI-H GI cancers. Three of seven patients (43%) had pCR and three others (43%) had notable partial responses. There is a need to understand IO-refractory primary tumors and the differing effects of IO in local versus metastatic disease. While our data is limited by sample size, larger clinical trials can establish the safety and utility of neoadjuvant IO, potentially sparing many patients from surgery. We will collaborate with other centers for a larger scale analysis on neoadjuvant IO in MSI-H GI cancers.

Ipi = ipilimumab; nivo = nivolumab; pembro = pembrolizumab ¹Initial colon cancer resected without adjuvant therapy. Local tumor recurrence was treated with neoadjuvant IO. ²Lymph nodes and a peritoneal nodule were initially concerning for metastases, but nodule was non-malignant on biopsy. ³Initial metastatic peritoneal washings cleared after neoadjuvant therapy. Tumor recurred 15 months after primary resection while on adjuvant pembro. ⁴Oligometastatic disease with a single liver metastasis. Cancer progressed on neoadjuvant IO, so the primary was not resected.