Table 2. Treatment characteristics and response to PD-1/PD-L1/CTLA-4 blockade.
| MSI-H or POLE-mutated | RAS/BRAF status | Prior therapy | Archival tissue, collection date | CI start date | Cycles of therapy | Overall best response | Duration of disease control^ |
|---|---|---|---|---|---|---|---|
| MSI-H* | RAS WT/BRAF WT | Definitive surgery, adjuvant capecitabine, XELOX, FOLFIRI-cetuximab, HIPEC (mitomycin C) and debulking surgery, FOLFOX-MEK162 | Cecum, 4/21/10 | 11/12/15 | 51 weeks | PR | 17.8 months (ongoing) |
| MSI-H | RAS WT/BRAFV600E MT | Definitive surgery, adjuvant capecitabine, FOLFIRI-bevacizumab | Cecum, 4/14/15 | 5/13/16 | 17 (ongoing) | CR | 11.7 months (ongoing) |
| MSI-H | RAS WT/BRAF WT | XELOX-panitumumab, surgery (palliative/debulking), FOLFIRI-cetuximab, FOLFOX-Ziv-aflibercept | Liver, 1/20/16 | 9/2/16 | 3 | PD | – |
| MSI-H | RAS WT/BRAF WT | FOLFOX-bevacizumab, definitive surgery and metastectomy, irinotecan-panitumumab | Cecum, 1/14/16 | 9/23/16 | 10 (ongoing) | PR | 7.4 months (ongoing) |
| MSI-H | RAS WT/BRAF WT | Definitive surgery (METS found on surgery), FOLFOX-bevacizumab, capecitabine-cetuximab, 5-FU/LV/bevacizumab, FOLFIRI-bevacizumab | Ascending colon, 3/17/15 | 8/12/16 | 3 | PD | |
| MSS/POLEP286R | RAS WT/BRAF WT | Surgery (palliative/debulking) | Sigmoid, 8/18/16 | 10/14/16 | 1 | PD | |
| MSS/POLEP286R | RAS WT/BRAF WT | Definitive surgery, adjuvant FOLFOX, FOLFIRI-bevacizumab | Cecum, 4/30/15 | 10/7/16 | 10 (ongoing) | SD | 6.9 months (ongoing) |
| MSS/POLEV411L | KRASN116H, N116T MT/BRAF WT | Definitive surgery, FOLFOX, FOLFIRI-bevacizumab | Ascending colon, 3/16/15 | 5/6/16 | 14 (ongoing) | CR | 12.0 months (ongoing) |
^, start of checkpoint inhibitor therapy to May 4, 2017; *, this is the only patient treated with an investigational PD-L1/CTLA-4 combination. All other patients received off label pembrolizumab monotherapy. MSI-H, microsatellite instability-high; CI, immune checkpoint inhibitor; WT, wild type; XELOX, capecitabine and oxaliplatin; FOLFIRI, 5-fluorouracil (5-FU), leucovorin (LV), and irinotecan; HIPEC, hyperthermic intraperitoneal chemotherapy; FOLFOX, 5-FU, LV, and oxaliplatin; MEK162, investigational MEK1/2 inhibitor; PR, partial response; MT, mutant; CR, complete response; PD, progressive disease; SD, stable disease.