Pembroliuzmab in gastrointestinal (GI) malignancies with defective DNA mismatch repair (dMMR): A single institution experience.

Abstract

792 Background: Defective DNA mismatch repair is associated with increased mutation load and expression of neoantigens. Increased activity of PD-1 inhibitor is reported in patients with GI cancers with dMMR. Here, we describe our experience at Huntsman Cancer Institute with PD-1 inhibition in subjects with GI malignancies with dMMR. Methods: Retrospective chart review of patients with metastatic GI malignancies with dMMR, treated with pembrolizumab at Huntsman Cancer Institute between July 15, 2015 and September 26, 2016. Results: A total of 9 patients were identified that received at least 1 dose of pembrolizumab (colorectal n=5; cholangiocarcinoma n=2; pancreatic n=2). Of the 9 patients, 5 received concurrent cytoxic chemotherapy. Median number of doses given was 3 (range 1 to 17). Three patients received pembrolizumab on clinical trial with concomitant mFOLFOX6. Five patients have restaging scans at the time of abstract submission. The first patient has cholangiocarcinoma and experienced a -73% response per RECIST criteria from baseline (time to progression +8 months). The second patient has pancreatic adenocarcinoma and showed a total -56.7% response per RECIST criteria from baseline (time to progression +5 months). The third patient has colorectal carcinoma and had stable disease by RECIST at restaging after 2 months (biochemical response with a 50% decrease in CEA). The fourth patient has cholangiocarcinoma and had a biochemical response with a 50% decrease in CA 19-9 and a mixed response on first restaging scan (time to progression +3.5 months). All 4 of these patients continue to have response to therapy at the time of abstract submission. The fifth patient who had colorectal cancer and died from upper GI bleeding. Restaging CT scans showed response to therapy after 6 weeks of treatment. Four additional patients initiated treatment recently and have yet to undergo restaging scans. Conclusions: Single-institution data seem to confirm activity of PD-1 inhibitor in GI malignancies that harbor dMMR. All 5 restaged patients demonstrated response to PD-1 inhibition by RECIST criteria or decreased tumor marker. Updated responses for all patients will be presented during the meeting.