Researchers concerned about younger adults succumbing to this deadly disease, prompting calls for even more innovative and aggressive treatments
SCOTTSDALE, Ariz. — July 16, 2024 — HonorHealth Research Institute is part of an international effort to create one of the first immunotherapy drug combinations to successfully treat colorectal cancer, which after lung cancer is the nation’s second leading cause of cancer-related death.
An estimated 53,000 Americans will die this year from colorectal cancer. Though generally seen in older adults, it is becoming more frequent among younger adults, those aged 20-50, who generally are not screened for this often aggressive cancer. Like all cancers, early detection leads to more successful patient outcomes.
“This was the first time immunotherapy has really been shown to be working in this most common type of colon cancer,” said Sunil Sharma, M.D., Chief of Translational Oncology and Drug Development at HonorHealth Research Institute.
Dr. Sharma is one of the authors of a three-year study of 148 patients worldwide published June 13 in the journal Nature Medicine, documenting the positive effects of a combination treatment of two immunotherapy drugs, botensilimab plus balstilimab, on microsatellite stable metastatic colorectal cancer, which is the most common type of colon cancer, and one that has generally not been responsive to immunotherapy.
The Research Institute was one of the first of the study’s more than dozen major research sites, and one with among the highest enrollments.
‘Immunotherapies can work’
“We’ve shown the proof of principle that immunotherapies can work against this disease. This creates a backbone upon which we can hopefully build even better immunotherapies,” said Dr. Sharma. “It sets us up to do even more combinations on top of this platform that seems to be working. Hopefully, we can actually have even better results in the future.”
This drug combination was well-tolerated by patients in the study.
Michael S. Gordon, M.D., Chief Medical Officer of HonorHealth Research Institute, noted that the Research Institute is focused on working towards earlier diagnosis in this patient population, using more up-to-date screening technologies to forestall this epidemic of cancer.
How immunotherapy works
Dr. Gordon, who also is an author of the research paper — Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: a phase 1 trial — said the combination immunotherapy is able to overcome the cancer’s attempt to hijack the body’s own immune system.
The combination of the two antibodies in the therapy sidestep what are known as immune checkpoint blockades, natural elements that ordinarily prevent immune cells from attacking healthy tissue, but which cancer cells also use to cloak themselves.
“If the immune system gets overly aggressive, it can attack the patient’s own body. But if the immune system is shut down, it can’t fight the cancer,” Dr. Gordon explained. “With this therapy, you wind up with larger numbers of highly effective immune T cells that can attack the cancer.”
The study found that the combination immunotherapy was most effective against cancer that had not metastasized or spread to the liver, citing this as a possible future target of investigation.
“For those patients without liver metastases, there appears to be a higher response rate and a prolonged interval of ongoing stable response lasting several years in some patients in contrast to those patients with liver metastases,” said Dr. Gordon, adding, “There is a unique opportunity for further research.”
Alarming incidence among young adults
A concern of Dr. Sharma was the surprising number of younger adults who are, for unknown reasons, developing this disease.
According to the paper in Nature Medicine: “Alarmingly, from 1995 to 2019, the number of patients under the age of 55 who were diagnosed with CRC (colorectal cancer) in the United States nearly doubled.”
“Oh my God, my whole clinic is full of younger people dying of colon cancer. It’s a real tragedy. It’s quite sad because they oftentimes present with advanced or metastatic disease. When they present with symptoms, nobody’s thinking they have colon cancer,” said Dr. Sharma, noting that their condition is often misdiagnosed as irritable bowel syndrome, hemorrhoids or something else, and screens such as colonoscopies usually aren’t recommended until patients are older than 45.
“They get treated late and so it becomes a very aggressive tumor. It’s a real problem,” said Dr. Sharma. “We may need even more aggressive treatment.”
Agenus Inc., the Lexington, Mass., based sponsor of the clinical trial, is planning to seek FDA approval of the combination immunotherapy and has initiated a phase 3 clinical trial.