Colon cancer was the fourth most common cancer in 2020, with almost 150,000 new cases diagnosed and a little more than 53,000 deaths related to this cancer. It was just behind breast, lung and prostate cancers in the number of cancer cases diagnosed in this country, according to Surveillance, Epidemiology and End Results Survey (SEER) data from the federal government.
While these statistics may be considered ‘grey clouds,’ the silver lining is that colon cancer patients now have new treatment options with immunotherapy, a type of therapy that uses the human immune system to fight tumor cells.
The immunotherapy agent Keytruda, also known by its scientific name Pembrolizumab, was approved by the FDA to treat colon/colorectal cancers on June 29, 2020, making it a first-line treatment for metastatic and resectable colon cancer (i.e., cancer that can be removed surgically).
“Immunotherapy had no part in colon cancer treatment before Keytruda’s FDA approval,” said Mohammed Najeeb Al Hallak, M.D., MS, member of the Gastrointestinal and Neuroendocrine Multidisciplinary Team at Karmanos Cancer Institute and assistant professor at Wayne State University School of Medicine. “This is a revolutionary approval.”
Keytruda is approved for subsets of patients with advanced colorectal cancer that has high microsatellite instability (MSI-High), a DNA mismatch repair deficiency, or high tumor mutational burden. In lay terms, MSI-High means that the tumor’s DNA cannot repair its own damage, causing the tumor to be surrounded by immune cells.
In clinical studies, the use of Keytruda, as opposed to chemotherapy, increased the median progression-free survival (surviving without cancer progression) of participants to 16.5 months compared to 8.2 months with chemotherapy alone.
Dr. Al Hallak is very excited about these results.
“With all the previous treatments used, none improved progression-free survival,” he said. “I had not seen a cure for Stage 4 colon cancer before immunotherapy. This is a doubling of the median progression-free survival as a first-line treatment.”
Keytruda, which was initially approved by the FDA in 2014, was initially used for advanced melanoma. It then gained approval for non-small cell lung cancer as a follow-up treatment after chemotherapy. Later, it received approval for use in metastatic head and neck squamous cell carcinoma. Since 2016, it has been approved for use in Hodgkin’s lymphoma, bladder cancer, cervical cancer, esophageal cancer, gastric and gastroesophageal cancers and advanced renal cell carcinoma.
Finally, Keytruda is having its day as a treatment for some types of colon cancer.
Keytruda, which is administered intravenously, is a type of immunotherapy known as an immune checkpoint inhibitor. Immune checkpoints are a normal part of the human immune system. Their role is to prevent an immune response from being so strong that it destroys healthy cells. The immune checkpoints engage when proteins on the surface of immune cells called T-cells recognize and bind to partner proteins on other cells, such as some tumor cells. These proteins are called immune checkpoint proteins.
“Pembrolizumab (Keytruda) inhibits PD1 and blocks the interaction between PD-1 and PD-L1 checkpoint proteins, which, if left to interact, would create a shield around the tumor cell, making it immune to T-cells,” Dr. Al Hallak said. When Keytruda intercepts that interaction, it removes the tumor cell’s shield, allowing T-cells to attack and kill the tumor cells.
Dr. Al Hallak is now hoping to move forward to utilize immunotherapy on most colorectal cancer patients for whom immunotherapy alone does not work.
“I hope that Keytruda, in combination with chemotherapy, will be approved for all colon cancer patients,” he said. “I think we’re going to see clinical study results soon. If those are positive, then this will bring more hope for most colon cancer patients to use Keytruda early in their treatment.”