Overcoming Stage IV Colon Cancer: Betty’s High-Mutation Journey

When 65-year-old Betty from British Columbia was first diagnosed with stage IV metastatic colon cancer, her doctors pursued the standard treatment path: surgery, then chemotherapy (FOLFIRI, FOLFOX), and finally an EGFR-targeted drug, panitumumab. Unfortunately, her disease continued to progress, and she endured multiple side effects without any real improvement. Convinced there had to be more options, Betty sought additional insights through the onco-panel tumor DNA sequencing pilot at the British Columbia Cancer Agency (BCCA).

These advanced tests revealed that Betty’s colon cancer fell into the CMS1 (microsatellite unstable/immune) subtype and, crucially, carried the BRAF V600E mutation. Although this genetic profile often signifies poor prognosis and resistance to many standard therapies—especially EGFR inhibitors—her tumors’ high mutation load also indicated that they could respond to immunotherapy. Armed with this new information, Betty underwent additional testing to confirm that she was MSI-High (microsatellite instability-high) and MMR-deficient (mismatch repair-deficient).

Given these findings, Betty started a PD-1 inhibitor, pembrolizumab. After several infusions, most of her tumors responded positively, showing reduced SUV levels in PET/CT scans. At first, her care team worried about “mixed” or new growths; however, this turned out to be pseudo-progression—a common scenario where newly recruited immune cells temporarily make lesions appear larger. To account for delayed responses, her team monitored her disease with liquid biopsy tests measuring the BRAF V600E mutation levels in her bloodstream.

Encouragingly, new evidence showed that combining pembrolizumab with the CTLA4 inhibitor ipilimumab could yield an even higher rate of disease control for patients like Betty. Her oncologist adopted this enhanced regimen, which has led to further improvements. Although her subtype is particularly challenging, Betty now has multiple immunotherapy and targeted treatment avenues to explore, offering renewed hope and significantly extending her survival without the debilitating side effects of repeated chemotherapy.