Study: Which Mesothelioma Patients Will Immunotherapy Benefit?
Thoracic surgeon Dr. Bryan Burt at the Baylor College of Medicine wants to better identify which patients with pleural mesothelioma cancer will benefit (and which will not) from promising immunotherapy drugs such as Keytruda and Opdivo.
No test currently exists to make that determination accurately, often leading to unnecessary treatments with adverse side effects and shattered hopes for mesothelioma patients and families.
The National Cancer Institute recently granted Burt and his team a five-year, $2.5 million MERIT Award to fund his study and develop a clinically relevant test to better predict treatment efficacy. “I think this is pretty important,” Burt told The Mesothelioma Center at Asbestos.com.
“Other [tests] have been tried, but have not been successful. We’re hopeful at this point,” he added. “We want to identify the patients who would have a meaningful response before they begin treatment.”
Eliminating Unnecessary Side Effects
An estimated 50% of those receiving immunotherapy agents known as checkpoint inhibitors see little or no benefit from the treatment. According to recent studies, approximately 20% see actual tumor shrinkage and another 30% experience a partial response and short-term stable disease.
The hope is that a more reliable test can save those unlikely to respond from the potentially serious side effects, such as kidney infection or lung inflammation. “This could help patients avoid ineffective treatment,” Burt explained.
Burt is chief of the Division of Thoracic Surgery and part of the Mesothelioma Treatment Program at Baylor, where he is an associate professor of surgery. He worked alongside legendary mesothelioma specialist Dr. David Sugarbaker, who died in 2018. They often talked about the lack of effective treatment options available for patients not eligible for surgery, which is approximately 75% of those diagnosed.
“Yes, this could potentially change the standard of care” Burt noted. “This is innovative, using novel technology to predict who will respond best.”
Following Recent FDA Approval
The study comes in the wake of the FDA granting historic treatment approval in October of the immunotherapy combination of Opdivo and Yervoy for mesothelioma patients. It was the FDA’s first systemic treatment approval for mesothelioma patients in 16 years. Keytruda was approved earlier in the year, but only for a select group of mesothelioma patients.
Burt is also the primary investigator of a phase II clinical trial at Baylor studying the effectiveness of using Opdivo and MTG201, a modified adenovirus designed to increase the effectiveness of certain immunotherapy drugs. The most effective treatment for pleural mesothelioma through the past decade has been a multidisciplinary regime involving surgery, chemotherapy and radiation, but only a small percentage of patients qualify.
Too often, the disease is already too far advanced, or patients are too frail to complete the regimen. The majority of patients receive only a combination of chemotherapy, leading to a median survival of less than a year.
The recent emergence of the immunotherapy checkpoint inhibitors has been hailed as a much-needed treatment breakthrough. They work by suppressing the molecules that often prevent the body’s natural immune response. Unfortunately, they don’t work for a large percentage of those diagnosed.
Novel, High Tech Analysis Required
Burt’s study includes a novel technique to analyze the presence of 30 different cell types from a small tumor sample. It also involves an architectural exam of tumor tissue.
“In addition to determining how many cells there are of each type, we also see how these cells are organized in the tumor. Are they close to blood vessels? Are they close to each other? Our preliminary data showed that tissue immune cell architecture also predicts response to treatment,” Burt said.
Drugs such as Opdivo and Keytruda work by overriding the inhibitors. This study also is designed to better understand the biological mechanisms affecting the immune system.
The goal is to use both the cellular organization and molecular pathways to develop a test that can predict the response to the checkpoint inhibitor drugs. Upon completion, a clinical trial would follow, in which treatment would depend on the results of the individual’s test.
“Within the next year or two, we’ll have a good idea of whether these components are working,” Burt said.