Anthony W. Tolcher, MD
At a time of rapid advancements in cancer biology and innovation, researchers are facing mounting challenges in finding enough patients to recruit for clinical trials. Although this has been difficult for many years, current trends in oncology drug development may be making the problem more acute.
The proliferation of targeted investigational drugs has both narrowed the pool of eligible patients and increased demand for them. In addition, trials are conducted more often at centrally located academic centers than at the community oncology offices where the vast majority of patients with cancer go for treatment. These factors make the study and approval of new drugs more expensive and time-consuming and leave many people who have treatment-resistant cancers without access to potentially life-saving therapies.
These challenges have spurred efforts to expand and diversify the pool of clinical trial participants. Medical organizations have called for the relaxation of eligibility criteria and investigators are working through community practice networks to reach more patients (Table
). Genomic testing companies, analytics firms, and drug makers are developing programs that collect patients’ data and connect them to appropriate studies, while working to bring trials to patients wherever they are rather than requiring them to travel long distances to benefit from new treatments.
Table. Key Considerations for Expanding Clinical Trial Eligibility6
“If we look at the data, historically less than 3% to 5% of patients actually get enrolled in clinical trials, and that doesn’t even account for the lack of diversity of patients,” said Arturo Loaiza-Bonilla, MD, chief of medical oncology and medical director of research at Cancer Treatment Centers of America in Philadelphia. “There are issues with patients older than 65, with racial minorities, and with populations of patients who don’t have access to academic centers to get treatment. It’s a very important issue and something that I look forward to seeing improve over time.”
Studies have consistently found that fewer than 1 in 20 adults with cancer enroll in clinical trials.1
And about one-fifth of drug studies accrue less than half of their target number of patients after 3 years, according to an analysis of phase II and phase III adult trials sponsored by the National Clinical Trials Network, a program of the National Cancer Institute (NCI).2
When a trial closes due to low accrual, the researchers cannot report on the results and advance the drug toward approval. Trials with greater risk of low accrual included those that required a biopsy and phase III randomized trials, as well as those that faced more competition from other trials for patients with the same condition.
Competing for Patients
A fundamental problem is that many potentially eligible patients never even reach the point of learning about a trial and deciding whether to participate. About 90% of patients are treated in the community setting and only 10% at academic centers, yet trials tend to be sited at the centers, said Anthony W. Tolcher, MD, of Texas Oncology and CEO and director of clinical research at NEXT Oncology, both in San Antonio.
“There’s a disconnect between where the studies are and where the patients are,” he said. Previously, “the expectation was that patients would come from all the surrounding areas to go onto NCI studies. That was fine when the National Cancer Institute used to be in the business of drug discovery and first-in-human type clinical studies, as well as cooperative groups, but that’s all changed. Almost every single new drug comes from biotech and the pharmaceutical industry.”
The shift to industry-sponsored research has generated a steady stream of more effective agents, revolutionizing cancer care, but the abundance of trials has overtaxed the pool of eligible patients at cancer centers, Tolcher said. The National Institutes of Health’s ClinicalTrials. gov database lists more than 8600 active cancer drug trials in the United States, including over 1000 for PD-1/PD-L1 inhibitors.3
Also, more than 240 immuno-oncology drugs were in development in 2017, according to Pharmaceutical Research and Manufacturers of America.4