Tanios Bekaii-Saab, MD, professor of medicine, Mayo Clinic, discusses the use of immunotherapy in patients with microsatellite stable colorectal cancer.
Tanios Bekaii-Saab, MD, professor of medicine, Mayo Clinic, discusses the use of immunotherapy in patients with microsatellite stable (MSS) colorectal cancer (CRC).
MSS tumors are like immune deserts, says Bekaii-Saab. There are no visible tumor-infiltrating lymphocytes (TILs), so the quest becomes how to increase the accessibility of TILs to where they should be so PD-1 inhibitors can perform effectively. One way that has been shown preclinically is through MEK inhibitors like cobimetinib (Cotellic).
The initial study with cobimetinib plus atezolizumab (Tecentriq) focused primarily on MSS tumors. These patients had a response rate of a little over 10%. Some patients had significant survival—not at the level of what is expected from PD-1 inhibitors, but certainly above what is expected from a PD-1 or MEK inhibitor alone.
There are other efforts underway in phase I/II trials looking at strategies to change the immune desert into an immune-infiltrated disease, says Bekaii-Saab. Those trials primarily focus on the MAPK/ERK pathway, but there are also other hints that the Wnt/beta-catenin pathways could also be manipulated through certain agents to increase the lymphocytic infiltrate.