Immune checkpoint inhibition in locally advanced rectal adenocarcinoma at Mayo Clinic.

Abstract

e15626 Background: Studies have shown the effectiveness of immune checkpoint inhibition (ICI) in patients with tumors demonstrating microsatellite instability (MSI-H) and an associated defect in DNA mismatch repair (dMMR). In particular, KEYNOTE-177 demonstrated significant survival benefit for patients with unresectable or metastatic colorectal cancer with MSI-H or dMMR. Recently published case reports and series have demonstrated similar outcomes for patients with locally advanced and resectable rectal cancer. We report on the experience of patients with locally advanced, resectable rectal adenocarcinoma treated across the Mayo Clinic Health System. Methods: We conducted a retrospective analysis of patients treated at Mayo Clinic since 2015 A search of the Mayo Clinic database was done to include parameters for confirmed rectal adenocarcinoma, dMMR in pathology reports. Patients receiving ICI treatment including pembrolizumab, nivolumab/ipilimumab and durvalumab in any combination with chemotherapy and/or radiation were included. Patients with metastatic disease at the time of surgical intervention or ICI were excluded. Clinical data was assimilated. Results: Twenty-one patients met criteria for inclusion in our analysis. Fifteen patients had de novo disease. Six patients had local recurrence and had been treated previously with chemotherapy, radiation (RT) and surgery. None of the patients included had prior ICI therapy. Fifteen patients had Lynch syndrome. The median age of diagnosis was 41.5 years. Seven patients underwent surgical intervention. of the seven patients received surgery upfront followed by immunotherapy. The remaining six had neoadjuvant immunotherapy alone or in combination with chemotherapy and/or radiation. Prior to surgery, all patients demonstrated radiographic partial response (rPR). 67% of these demonstrated a pathologic complete response (pCR) while 33% had residual disease. The patient who received surgery upfront and adjuvant ICI continues to have radiographic stable disease after 1 year of treatment. For patients who did not have surgery, 50% had radiographic “complete or near complete” response (rCR), 43% had rPR and 7% had radiographic stable disease. Ten patients received RT and ICI with 70% demonstrating rCR and 30% rPR. Overall, the objective response rate was 90 Response to treatment was observed upwards of 75 months. Only 1 person in the study had progression of disease that occurred after 14 months of therapy. Conclusions: Similar to KEYNOTE-177, patients with locally advanced MSI-H/dMMR rectal cancer have significant and durable response to immunotherapy alone or in combination with chemotherapy, radiation and surgery. Further large prospective trials are needed to validate these findings and determine a standardized approach.