Response to pembrolizumab in patients with mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC).

714 Background: Mismatch repair deficient (dMMR) colorectal cancer (CRC) has been shown to be responsive to blockade with anti-programmed death-1 (PD-1) antibodies. We describe a cohort of 17 patients with dMMR mCRC receiving treatment with pembrolizumab. Methods: Patients were identified through review of the Mayo Clinic electronic medical record (EMR) and chemotherapy administration records from May 2015 through September 2016. All patients with dMMR mCRC who received treatment with pembrolizumab were included. The EMR was reviewed to identify demographic, clinical, pathologic and treatment details. Overall survival (OS), progression free survival (PFS) and disease control rate (DCR=CR+PR+SD) are reported. Time to event analysis was calculated using the Kaplan-Meier method. Results: A total of 17 patients were included in this analysis; median age at diagnosis was 48.5 years (range 25-93); 59% were female. Most primary tumors were right sided (n=12; 71%), 4 (24%) were left sided and 1 (5%) was a tumor of unknown primary within the bowel. Thirteen (75%) patients received 2 or more lines of therapy prior to pembrolizumab (range 1-4). All patients received 2 mg/kg every 3 weeks, with the exception of two patients on a clinical trial; one who received 200 mg every 3 weeks, the other received 10 mg/kg every 2 weeks. The most common mutations (mut) identified were loss of MLH1 (9/12) and PMS2 (10/12), 4 patients had germline mut. KRAS mut was identified in 6/15 patients and only 1 patient had BRAF mut. Number of cycles of pembrolizumab ranged from 1 to 35, with 10 (59%) patients receiving 6 or more cycles. DCR at first assessment was 57%, with 7% CR and 50% PR. Median follow-up was 28 months (95% CI 18-55). Median OS was 103 months (95% CI NR-NR); 12-month OS was 88% and 24-month OS was 81%. Median OS post-PD-1 therapy was NR (95% CI 2-NR). Median PFS was 19 months (95% CI 5-19); 12-month PFS was 64% and 24-month PFS was 0%. At time of analysis, 11 patients remain on PD-1 therapy; 4 patients have died. Conclusions: Anti-PD1 blockade with pembrolizumab can provide long lasting benefit in dMMR mCRC, even in heavily pretreated patients.