Colorectal cancer, also known as bowel cancer, is the third most common cancer worldwide and the second leading cause of cancer deaths. Treatments typically include surgery, radiotherapy, chemotherapy, or immunotherapy, but their efficacy varies depending on the type of bowel cancer.
A recent phase 1 trial has found that a combination of two monoclonal antibodies, botensilimab and balstilimab, could be effective against a common form of colorectal cancer that has historically not responded to immunotherapy. These findings could pave the way for more effective treatments for this type of cancer.
Understanding colorectal cancer
According to the World Health Organization, around 10% of cancers worldwide are colorectal cancer. In the United States, the American Cancer Society estimates that more than 150,000 people will be diagnosed with colon or rectal cancer in 2024.
The risk of colorectal cancer increases with age, with most cases diagnosed in people over 50. The causes are believed to be a combination of genetic and environmental risk factors, including:
- Male sex
- A diet low in fiber and high in animal protein, particularly red and processed meats, and saturated fats
- Overweight or obesity
- Smoking and alcohol consumption
- Low levels of physical activity
- Inflammatory bowel disease
New hope with immunotherapy
Immunotherapy has shown effectiveness against only some types of colorectal cancer. However, the new trial found that the combination of botensilimab and balstilimab was effective in 61% of people with advanced microsatellite stable metastatic colorectal cancer (MSS mCRC), a form previously resistant to immunotherapy.
Professor Justin Stebbing of Anglia Ruskin University, U.K., and the study’s lead author, stated, “It’s the first time we’ve consistently seen durable responses in heavily pre-treated patients with colon cancer, so I think it’s hugely exciting, especially as this affects so many people.”
Study findings
The trial involved 148 patients with solid bowel tumors that had metastasized. They were initially treated with escalating doses of botensilimab, followed by a combination of botensilimab and balstilimab. Of the 101 patients who completed the six-month follow-up, 62 showed some response to the treatment.
Dr. Daniel Landau, an oncologist not involved in the study, commented, “There has been a lot of interest in developing immunotherapies that can work for these cancers too. Botensilimab plus balstilimab may be the answer we’ve been searching for.”
Challenges and future directions
The study also found that patients with liver metastases had significantly lower response and survival times. Stebbing explained, “We know that disease in the liver can have specific effects on the immune system, so as these drugs work by harnessing the activity of specific T cells to fight cancer, it’s possible that liver disease can affect the treatment in that way.”
While the trial’s early results are promising, further studies are needed to verify these findings. Stebbing voiced optimism, stating, “For the 95% of patients diagnosed with MSS mCRC, there are no approved immunotherapies, making long-term survival exceedingly rare. I hope this changes that.”
Overall, this new combination therapy offers a glimmer of hope for those battling advanced colorectal cancer, potentially leading to more effective and targeted treatments in the future.
