Clinical Trial Exclusions: Are Researchers Missing Out?

Clinical trials are the driving force behind cancer advancements, though many patients are excluded from participating in them — especially if they are investigating immunotherapy agents, explained Mohammad Jahanzeb, M.D.

“Clinical trials have very rigorous criteria. When we think of immunotherapy trials, they specifically don’t want to anger an immune system that’s already angry. So naturally, patients with autoimmune disease are excluded,” Jahanzeb said, adding that patients who had solid organ transplants or allogenic bone marrow transplantation are also excluded, in fear that the drug being tried may make their body reject their transplant.

Jahanzeb, a professor of medicine and hematology/oncology at the University of Miami Sylvester Comprehensive Cancer Center, recently discussed real-world eligibility for immunotherapy trials at the 16^th Annual Winter Lung Cancer Conference in Miami, Florida.

“At the end of the day, only about 4 percent of the adult population of patients is treated on clinical trials in the United States, as opposed to nearly 90-plus percent of children with cancer,” he said.

Jahanzeb also listed other patient characteristics that are likely to get them excluded from a clinical trial. They included: having other cancers, poor performance status, HIV, hepatitis, psychiatric conditions and drug additions.

While researchers stopped putting age limits on clinical trials, there may still be some inherent bias against older individuals.

“We have a bias against the elderly, even though politically correctly, we don’t put age limit in the protocol. We used to. It was fair game two decades ago,” Jahanzeb said.

Previously, researchers agreed that 65 is the divide between elderly and non-elderly — something that may have come out of the Medicare eligibility age, according to Jahanzeb. But newer studies are upping the threshold to 70 years of age – a sensical move since the average age of lung cancer diagnoses is 68.

Looking specifically at different age brackets in clinical trials could prove beneficial, Jahanzeb said. He mentioned the CheckMate-017 trial, which compared Opdivo (nivolumab) to docetaxel in previously treated advanced or metastatic squamous cell non-small cell lung cancer (NSCLC).

“(Results) showed no benefit in the older population. But when you subset it, patients from 65 to 75 actually derived greater benefit,” Jahanzeb said. “But it was patients older than 75 who seemed to be having detrimental effect with immunotherapy. So, in the end it seemed to be a wash, but that’s squamous histology.”

Gathering real-world data that is not from clinical trials is also crucial, Jahanzeb said, emphasizing the importance of patient registries.

“I think we should make attempts to gather the data because there’s only a sliver of the population that is treated on clinical trials, and then we take that information and apply it to everybody,” he said.

Larger registries may bring to light rare side effects. “If something happens one in 2,000 times, we may not catch it in a 1,000-patient trial, and we may need a 5,000-patient database to find those rare side effects.”

Getting a better understanding of how these drugs work — both for those on clinical trials and for the general population – is crucial, especially since immunotherapy may be the way forward for many patients with lung cancer.

“I think that immunotherapy is now an integral part of lung cancer treatment,” Jahanzeb said. “It is what platinum (therapies) used to be — the backbone of all therapy.”