P-34 Real-world Efficacy and Safety of Immune Checkpoint Inhibitors in Microsatellite Unstable or Mismatch Repair Deficient Gastrointestinal Tumors

Immune checkpoint inhibitor (ICI) therapy is highly effective in mismatch repair deficient(dMMR)/microsatellite unstable (MSI-H) gastrointestinal tumors. In this study, we evaluated the efficacy and safety of ICI in dMMR/MSI-H gastrointestinal tumors in the real-world setting. We conducted a retrospective, multicentre, observational study of patients (pts) with MSI-H or dMMR gastrointestinal tumors treated with ICI at 6 hospitals from the Galician Research Group on Digestive Tumors (GITuD). We recorded 41 pts treated between October 2017 to March 2021. Median age was 67.9 years (range 35 – 87 years), 58.5% female, 80.5% ECOG PS0-1, 65.9% high grade, 39% synchronous presentation, 73.2% primary tumor resection, 19.5% >3 metastatic locations and 43.9% liver metastases. 73.2% had loss of expression of MLH1 and 14.6% identified germline mutations. Tumor location: 61% CRC (68% right-sided, 32% BRAFV600mt), 24.4% gastroesophageal adenocarcinoma, 4.9% pancreatic adenocarcinoma, 4.9% small bowel, 2.4% esophageal squamous cell carcinoma, 2.4% unknown origin. 39.1% of pts received ICI treatment in first-line (including 22% pts that had received adjuvant treatment previously), 34.1% in second-line and 26.8% in third-line or later. According to type of ICI, monotherapy with anti-PD-1 (pembrolizumab or nivolumab) was administered in 97.6% of pts, while 3.4% of them received a combination of anti-CTLA-4 and anti-PD-1. Median cycles received were 7 (range 1-52+ cycles). 36 pts (87.8%) were evaluable for response. Overall Response Rate (ORR) was 69.4% (CRC 69.6 % and no CRC 69.2%) and disease control rate (DCR) was 86.1% (CRC 87% and no CRC 84.6%). With a median follow up of 16 months, median PFS and OS were NR for CRC tumors and 20.2 months (95% CI, 3.8-36.7 months) and 20.2 months (95% CI, 8.6-31.8 months) for no CRC tumors, respectively. The most common grade 3-4 toxicities were: 4.9% nephritis, 2.4% pneumonitis, 2.4% asthenia, and 2.4% hepatitis. 7.3% discontinued treatment due to toxicity. No treatment-related deaths occurred. Our series confirms the efficacy and safety of ICI in dMMR/MSI-H gastrointestinal tumors in the real-world setting.