That MSI high.

Top Line: We learned at ASCO 2020 that first-line pembrolizumab was superior to chemotherapy for patients with MSI-high or mismatch repair deficient (dMMR) metastatic colorectal cancer.

The Study: Now we have those results in full publication. MSI-high tumors seem to be less sensitive to chemo. These tumors have a high mutational burden, though, which we’ve learned makes them more responsive to immunotherapy. In KEYNOTE-177, patients were randomized to pembro versus chemo. Chemo regimens were mFOLFOX6 or FOLFIRI—both with the option of additional bevacizumab or cetuximab. We already knew that median PFS was improved from 8.2 → 16.5 months. And at 24 months, the PFS rate was improved from 18.6 → 48.3%. As we’ve seen time and again, the benefit of immunotherapy over chemo in certain populations is driven by more durable responses. Pembro had a higher rate of response (33 → 43%) and a longer median duration of response. At the 2-year mark, a whopping 83% of partial/complete pembro responses were ongoing compared to just 35% for chemotherapy.  

TBL: Pembrolizumab results in higher, more durable response rates that improve progression-free survival for patients with MSI-high colorectal cancer. | Andre, N Engl J Med 2020