ISLAMABAD, June 21 (ONLINE): Colorectal, or bowel, cancer is the third most common cancer worldwide, and the second leading cause of cancer deaths.
\nTreatments include surgery, radiotherapy, chemotherapy, or immunotherapy, but the efficacy of treatment depends on the type of bowel cancer the person has.
\nA phase 1 trial has found that two monoclonal antibodies could be effective against a common form of colorectal cancer that has, historically, not responded to immunotherapy.
\nThese findings could be a first step towards more effective treatment for people with this form of colorectal cancer.
\nAccording to the World Health Organization, around 10%Trusted Source of cancers worldwide are colorectal (bowel) cancer. In the United States, the American Cancer Society estimates that more than 150,000 peopleTrusted Source will be diagnosed with cancer of the colon or rectum in 2024.<\/p>\n
The risk of colorectal cancer increases with age, and most cases are diagnosed in people over the age of 50. The cause is not clear, but is thought to be a combination of genetic and environmental risk factors, including:<\/p>\n
Male sex
\nA diet low in fiber, and high in animal protein, particularly red and processed meats, and saturated fats
\nOverweight or obesity
\nSmoking and alcohol consumption
\nLow levels of physical activity
\nInflammatory bowel disease.
\nTreatment is more effective if the cancer is detected early, and may include surgery to remove the tumor, radiation therapyTrusted Source or chemotherapyTrusted Source to destroy cancer cells and shrink the tumor, and immunotherapyTrusted Source.<\/p>\n
However, immunotherapy is effective against only some types of colorectal cancer. Now, a phase 1 trial has found that a combination of two monoclonal antibodies \u2014 botensilimab and balstilimab \u2014 was effective in 61% of people with advanced MSS colorectal cancer.<\/p>\n
The study is published in Nature MedicineTrusted Source.<\/p>\n
Justin Stebbing, professor of biomedical sciences at Anglia Ruskin University (ARU), U.K., and communicating author of the study, told Medical News Today:<\/p>\n
\u201cIt\u2019s the first time we\u2019ve consistently seen durable responses in the heavily pre-treated patients with colon cancer, so I think it\u2019s hugely exciting, especially as this affects so many people.\u201d<\/p>\n
Hard-to-treat cancers
\nAll the patients in the study had microsatellite stable metastatic colorectal cancer (MSS mCRC). This common form is sometimes referred to as \u2018immune coldTrusted Source\u2019 as, unlike other forms of colorectal cancer, it has previously proved resistant to immunotherapy.<\/p>\n
\u201cIt opens the door for immunotherapy to work in \u2018cold tumors\u2019, either those cancers that typically don\u2019t respond to immunotherapy, or even those who have previously responded and done well, but then it\u2019s stopped working. So it potentially has very broad applicability across tumor types,\u201d Prof. Stebbing told Medical News Today.<\/p>\n
In this study, the researchers recruited 148 patients with solid bowel tumors that had metastasizedTrusted Source (spread to other parts of the body). All had undergone several previous treatments for their cancer.<\/p>\n
They treated them initially with escalating doses of botensilimab, then with a combination of botensilimab and balstilimab.<\/p>\n
Of the total cohort, 101 patients completed the six-months follow-up required for the evaluation of the treatments.<\/p>\n
Encouraging results from immunotherapy against colorectal cancer
\n\u201cIn cancers that are shown to have broken repair mechanisms (MSI high or dMMR), it is known that immunotherapy can help. These immunotherapies allow the body\u2019s natural immune system to better recognize cancer cells and attack them. [\u2026] However, immunotherapy has generally been ineffective in cancers than have intact repair mechanisms [such as MSS mCRC].\u201d<\/p>\n
\u2014 Dr. Daniel Landau, oncologist, hematologist and contributor for The Mesothelioma Center at Asbestos.com, who was not involved in the study.<\/p>\n
The researchers reported \u2018encouraging efficacy\u2019 across different tumor types in the trial. They looked at several endpoints, including complete and partial response to treatment.<\/p>\n
Following combined therapy, 62 of the 101 patients showed some response, as Stebbing explained:<\/p>\n
\u201cOf the patients in the phase 1 trial, 101 took part in a six-month follow-up and of these, 61% of them saw their tumor shrink or remain stable after receiving a combination of botensilimab and balstilimab.\u201d<\/p>\n
Landau welcomed the findings:<\/p>\n
\u201cThere has been a lot of interest in developing immunotherapies that can work for these cancers too. Botensilimab plus balstilimab may be the answer we\u2019ve been searching for.\u201d<\/p>\n
Liver tumors reduced treatment efficacy
\nSome patients had metastases on their livers, so the researchers investigated whether this affected their response to the treatment.<\/p>\n
They found that in people with active liver metastases, response and survival times were significantly lower than in those without liver metastases.<\/p>\n
Stebbing explained why:<\/p>\n
\u201cWe 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\u2019s possible that liver disease can affect the treatment in that way.\u201d<\/p>\n
\u201cIt appears that folks with liver disease didn\u2019t respond as well. This could be for several reasons. Unfortunately, when the disease makes the leap into the liver, it is often more aggressive and more difficult to treat,\u201d Landau added.<\/p>\n
\u201cTraditional chemotherapies may be more important for this population. As more studies are done, we will better understand how the combination works and when it\u2019s best used,\u201d he told MNT.<\/p>\n
Manageable side effects
\nMany cancer treatments have severe side effects, but immunotherapy is generally tolerated better than some other treatments, such as chemotherapy.<\/p>\n
In this study, 89% of participants reported treatment-related adverse effects (TRAE), including fatigue, diarrhea and pyrexia (raised body temperature). In total, 52 people experienced serious TRAEs, but there were no treatment-related deaths during the study.<\/p>\n
Landau emphasized that this was to be expected:<\/p>\n
\u201cThe primary purpose of a phase 1 study is to find the safety of medications or combinations. [\u2026] At least in early results, most patients were able to tolerate the combination of botensilimab and balstilimab. The side effects seem to be fairly typical for immunotherapies, and most people tolerate immunotherapies better than chemotherapies.\u201d<\/p>\n
Promising early findings, but further research needed
\n\u201c[This trial] focuses on the efficacy and safety of botensilimab (BOT), an Fc-enhanced anti-CTLA-4 antibody, in combination with balstilimab (BAL), an anti-PD-1 antibody. Together, these therapies are designed to activate the immune system against a cancer type historically resistant to immunotherapy.\u201d<\/p>\n
\u2014 Prof. Justin Stebbing<\/p>\n
Landau explained that these early findings will need to be verified in further trials:<\/p>\n
\u201cIn a small study designed to look at the safety of this combination, it appears there was a response to the therapies in this population. However, it is important to understand that this was a very small study, so larger studies that compare this finding need to be conducted,\u201d he said.<\/p>\n","protected":false},"excerpt":{"rendered":"
ISLAMABAD, June 21 (ONLINE): Colorectal, or bowel, cancer is the third most common cancer worldwide, and the second leading cause of cancer deaths. Treatments include surgery, radiotherapy, chemotherapy, or immunotherapy, but the efficacy of treatment depends on the type of bowel cancer the person has. […]<\/p>\n
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