Journal
CLINICAL COLORECTAL CANCER
Volume 17, Issue 4, Pages 258-273Publisher
CIG MEDIA GROUP, LP
DOI: 10.1016/j.clcc.2018.06.004
Keywords
Immunogenic cell death (ICD); Immunotherapy; Microsatellite instability; PD-1; Tumor microenvironment
Categories
Funding
- NCI [P30 CA147904, UM1 CA099168]
- NATIONAL CANCER INSTITUTE [P30CA047904] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Metastatic colorectal cancer (mCRC) continues to be associated with a poor prognosis, and there remains a significant unmet need for novel agents and treatment regimens. Major breakthroughs have been made with immune checkpoint blockade therapy in several disease types, including DNA mismatch repair deficient/microsatellite instability-high (MSI-H) tumors. To date, however, immune checkpoint monotherapy has not shown significant clinical activity in the treatment of patients with mismatch repair proficient (pMMR)/non-MSI-H mCRC. The immune resistance mechanisms in pMMR/non-MSI-H mCRC have not yet been clearly elucidated. Significant efforts are currently focused on identifying effective combination immunotherapy regimens for the treatment of patients with pMMR/non-MSI-H mCRC. The combination of ate-zolizumab with cobimetinib had shown promising clinical activity in an early-phase clinical trial. Unfortunately, the IMblaze 370 (COTEZO) phase III trial of atezolizumab/cobimetinib combination in patients with mCRC failed to show significant improvement in overall survival in patients treated with the atezolizumab/combimetinib combination in comparison with regorafenib alone. This review summarizes the recent major advances in the clinical development of immunotherapy regimens for patients with pMMR/non-MSI-H mCRC. (C) 2018 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available