An increased interest in immunotherapy as a treatment for colorectal cancer has developed due to the identification of key molecules and the improved understanding of the interactions between the immune system and tumors. Immunotherapy can be a powerful weapon to treat cancer as it can be used to engage a patient’s own immune system to fight the disease. Depending on the mechanisms of action, immunotherapies can potentially be combined with other immunotherapeutics, chemotherapy, targeted therapy, or other traditional therapies. The recent discovery of immunotherapy agents such as checkpoint inhibitors has opened the door for treatment approaches that take advantage of the activity of these agents in various epithelial tumors. This can mean a great deal for advancing colorectal cancer management.
Colorectal cancer is the second most common cancer in female patients and the third most common in male patients. More than 20% of patients already have metastatic disease at the time of diagnosis. The survival rate with distant metastasis is approximately 12%; the average survival for advanced disease is about 30 months. Metastatic colorectal cancer is still the fourth most common cause of death from cancer. Consequently, pursuit of improved disease management for colorectal cancer with immunotherapy agents such as checkpoint inhibitors may be valuable and promising.
Checkpoint proteins of the immune system help keep immune cells from attacking other normal cells. Immune checkpoint inhibitors are agents that prevent immune cells from being turned off by cancer cells. The boosted immune response can help fight the attacking cancer and can result in a remarkable clinical response as a result. Thorough evaluation of the clinical activity of checkpoint inhibitors in colorectal cancer still needs to be conducted in larger patient groups, in trials that incorporate examination of predictive biomarkers, as well as combination of these agents with conventional therapies. Side effects have been noted and could be due to checkpoint inhibitors allowing the immune system to attack non-cancerous organs in the body. Fatigue, cough, nausea, skin rash, and itching have been the most common. Serious problems in the lungs, intestines, liver, kidneys, hormone-making glands, or other organs may also occur, as well as peculiar autoimmune adverse events, such as colitis, hepatitis, and endocrinopathies for checkpoint inhibitors such as ipilimumab and nivolumab.
The demonstrated effectiveness of immunotherapies in a broad range of solid malignancies shows great promise for treating colorectal cancer. Going forward, the development of reliable, predictive biomarkers and evolving the understanding of the mechanisms that underlie resistance or lack of response to immunotherapeutics are challenges to overcome. In order to gain further insights relevant to future investigations of colorectal cancer immunotherapy, new immunotherapies and approval of more drugs are needed and highly anticipated.
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Salvatore Volpe, MD, FAAP, FACP, CHCQM
Chief Medical Officer