Colorectal cancer is the third most common cancer diagnosed in women and men in the United States. While surgery and chemotherapy are the mainstays of treatment for colorectal cancer, some patients with the disease can be treated with immunotherapy.
What is immunotherapy?
Immunotherapy harnesses the individual’s immune defenses to fight cancer. In the case of colorectal cancer, the specific type of immunotherapy treatment used are checkpoint inhibitor drugs, which remove the brakes on the immune response that cancer has exploited to avoid the immune attack.
Who can be treated with immunotherapy for colorectal cancer?
So far, these immunotherapies are applicable to a small minority of patients with metastatic colorectal cancer. These are patients whose tumors have been tested and found to have specific genetic changes known as microsatellite instability (MSI-H) and mismatch repair deficiency (dMMR). These genetic changes create a predisposition for cancer cells to have high rates of DNA mutations, some of which may lead to the production of many abnormal antigens that can be targeted by the immune system. However, only about 5% of all patients with metastatic CRC have these genetic changes in their tumors.
Results of a clinical trial in June 2020 showed that patients with advanced colorectal cancer with MSI-H/dMMR genetic changes who were initially treated with an immune checkpoint inhibitor, pembrolizumab (Keytruda), had progression-free survival that was twice as long compared to standard chemotherapy. Based on these results, the U.S. Food and Drug Administration approved pembrolizumab as initial therapy for MSI-H colorectal cancer in June 2020. Oncologists said this development has the potential to change the standard of care for these patients.
Although immunotherapy in metastatic colorectal cancer is limited to the small minority with specific genetic changes, ongoing studies are investigating the role of immunotherapy in all stages of colorectal cancer and using combination treatment to enhance immune response regardless of whether those genetic changes are present, according to a recent review of the field.
About the Medical Reviewer
Dr. Rahma received his medical degree from University of Damascus in 1998. He completed his residency in Internal Medicine at East Carolina University followed by Geriatrics Fellowship at University of Hawaii. Dr. Rahma joined the National Cancer Institute (NCI) as an Immunotherapy Research Fellow in the Vaccine Branch in 2009 and completed a Fellowship in Medical Oncology in 2013 specializing in Cancer Immunotherapy and Gastrointestinal (GI) Oncology. Prior to joining Dana-Farber Cancer Institute, Dr. Rahma was the co-leader of the Hepatobiliary and Pancreatic Cancer Program at University of Virginia where he led translational research efforts as the Principal Investigator of many clinical trials.
Dr. Rahma is currently a Principal Investigator at the Center for Immuno-Oncology and Gastroenterology Cancer Center at Dana-Farber Cancer Institute. His research focus is on drug development of combinational immune therapeutics with the goal of moving immunotherapy to GI cancers and understanding the resistance mechanism to immunotherapy in GI cancers. He is currently the national lead of many studies combining immune checkpoint inhibitors and standard of care including chemotherapy and radiation therapy in addition to many novel combinations. Dr. Rahma also leads the Immune Toxicity Work Group at Dana-Farber, a unique program that is devoted to mitigating immune related toxicities.