'Nature Medicine' study, published this week, shows immune checkpoint inhibitor drug therapy, followed by traditional cancer treatment and tumor removal, improved patient survival rates for one of the world's deadliest cancers
PITTSBURGH, March 19, 2024 /PRNewswire-PRWeb/ -- Researchers from Allegheny Health Network (AHN), Baylor Scott & White Health, and Johns Hopkins Medicine have found that two newly approved immunotherapies can help to improve two-year survival rates for patients with gastroesophageal cancers.
Their findings were published this week in Nature Medicine, the world's leading multidisciplinary science journal.
In the U.S., gastroesophageal cancers are rare – about 22,000 people will be diagnosed this year—but they have a lower survival rate than most other cancers, because gastroesophageal cancer symptoms also mimic common indigestion symptoms, such as bloating, nausea and heartburn.
As a result, gastroesophageal cancers are typically discovered at more advanced stages.
"This seminal study supports the advancement of promising neoadjuvant doublet immunotherapy approaches to capture maximum therapeutic efficacy in patients afflicted with gastroesophageal cancers," said Ali H. Zaidi, MD, medical director of aerodigestive research at the AHN Cancer Institute, professor of surgery and medicine at Drexel University College of Medicine, and a first co-author of the study. "This is often a debilitating disease with limited treatment options, and these new findings give hope for the future."
In cancer medicine, "neoadjuvant" refers to complementary forms of treatment that occur before the primary treatment regimen. In this case, AHN, Baylor Scott & White, and Johns Hopkins researchers evaluated whether immune checkpoint inhibition medications, delivered prior to a gastroesophageal tumor surgical removal, would improve outcomes.
Immune checkpoints are a key part of the human immune system. Their role is to act as a brake on the system, preventing an immune response from being so strong that it destroys healthy cells in the body.
These immune checkpoints engage when proteins on the surface of immune cells, called T cells, recognize and bind to partner proteins on other cells – in some cases, tumor cells. These proteins are called immune checkpoint proteins.
When the checkpoint and partner proteins bind together, they send an "off" signal to the T cells, preventing the immune system from destroying potentially harmful cells or germs.
But immunotherapy drugs called immune checkpoint inhibitors (ICIs) work by blocking checkpoint proteins from binding with their partner proteins. This prevents the "off" signal from being sent, allowing the T cells to kill foreign cancer cells.
For the AHN, Baylor Scott & White, and Johns Hopkins clinical study, researchers looked at two different courses of neoadjuvant immunotherapy for patients with stage 2 or stage 3 gastroesophageal cancers – one involving a single checkpoint inhibition drug combined with chemotherapy and radiation therapy prior to tumor removal, and another involving two inhibitor drugs combined with chemotherapy and radiation therapy prior to tumor removal.
Notably, the two-drug therapy – relatlimab and nivolumab, a combination already utilized for treating melanoma – resulted in improved two-year progression-free rates (survival without their disease worsening) and overall survival rates for patients, according to the Nature Medicine paper.
In addition to the improved two-year survival rates, researchers monitored the efficacy of the therapy in real time and at a molecular level by analyzing blood samples to detect circulating tumor DNA (ctDNA).
They found that, after the ICI therapy, the amount of tumor DNA circulating in the blood appeared to be undetectable for most patients attaining a longer recurrence-free and overall survival, suggesting the individual's immunotherapy treatment had been effective.
Blood tests known as liquid biopsies can help doctors determine whether an immunotherapy regimen should be continued or de-escalated. If ctDNA levels are undetectable, that means the therapy is working, and treatment can be escalated. If ctDNA levels are still present, or if the patient is experiencing other side effects of immunotherapy, the therapy can be stopped.
The findings from the serial liquid biopsy analyses, led by study senior author Dr. Valsamo Anagnostou, MD, PhD, associate professor of oncology, Johns Hopkins School of Medicine, suggest that tests to determine ctDNA status and residual disease shortly after immunotherapy induction can be an important indicator for treatment escalation or de-escalation, ultimately maximizing therapeutic benefit.
"This supports the use of liquid biopsies for patient stratification early on in treatment, and can be generalized across cancer management plans," said Dr. Zaidi.
In addition to Dr. Zaidi, other AHN co-authors of the study included Blair Jobe, MD, chair of the AHN Esophageal Institute; Benny Weksler, MD, system director of Thoracic Surgery at AHN; Ali I. Amjad, MD, medical oncologist at AHN.
Researchers from AHN, Johns Hopkins Medicine, the Johns Hopkins School of Medicine, Baylor Scott & White, and the Sidney Kimmel Comprehensive Cancer Center were the paper's leader authors.
Bristol Myers Squibb, which manufactures nivolumab and relatlimab, sponsored the trial, which was independently initiated and jointly developed by AHN, Baylor Scott & White, and Johns Hopkins.
About the Allegheny Health Network – and the AHN Cancer Institute
Allegheny Health Network is a western Pennsylvania-based integrated healthcare system that serves patients from across a five-state region that includes western Pennsylvania and the adjacent regions of Ohio, West Virginia, Maryland, and New York. The Network's Cancer Institute employs more than 200 physicians and 500 oncology professionals who provide a complete spectrum of oncology care at 24 affiliated oncology clinics, including access to state-of-the-art technologies and new therapies being explored in hundreds of clinical cancer trials. The Cancer Institute has the only cancer program in the Pittsburgh region accredited as an Integrated Network Cancer Program by the American College of Surgeons Commission on Cancer, and its radiation oncology program is the largest in the country accredited by the American Society for Radiation Oncology. AHN Cancer Institute is a Quality Oncology Practice Initiative certified practice, and is accredited by the Foundation for Accreditation of Cellular Therapy, National Accreditation Program for Breast Centers and the National Accreditation Program for Rectal Cancer.
Media Contact
Emily Beatty, Allegheny Health Network, 5136789620, [email protected], www.ahn.org
SOURCE Allegheny Health Network
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