In the first comprehensive analysis of clinical trial enrollment among older adults with blood cancers, researchers from the U.S. Food and Drug Administration (FDA) found significant gaps in participation among those aged 75 and older when considered against the incidence of these malignancies in this age group, according to research being presented today during the 59th American Society of Hematology (ASH) Annual Meeting and Exposition in Atlanta. By comparison, adults under 65 years tend to be overly represented in these trials, despite the fact that a majority of blood cancers are most frequently diagnosed in those over 65 years of age.
"Until now, there has been very little information about the enrollment of adults with hematologic cancers. Based on our findings, the occurrence of cancer is much higher in adults over 75 years of age compared with the proportion of patients in this age group who enroll in clinical trials," said lead study author Bindu Kanapuru, MD, medical officer in the Division of Hematology Products, Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. "With so few patients aged 75 or older enrolled in clinical trials, critical information on the safety and effectiveness of new therapies in this age group is greatly lacking."
The magnitude of the disparity is particularly concerning given that the number of adults aged 75 and older who are diagnosed with blood cancers is only expected to rise as the population ages. Currently, one out of five patients diagnosed with most blood cancers is age 75 and above.
In this study, FDA researchers analyzed data on more than 44,000 patients who were enrolled in clinical trials of drug treatments for blood cancers that were evaluated by FDA as part of the drug approval process between 2005 and 2015.The researchers grouped patients by disease and age (<65, 65-74,and ≥75 years) and then compared their rates of enrollment in clinical trials to the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute 2010-2014 data on the rate of occurrence of each cancer by age group. Most patients were enrolled in trials of treatments for lymphoma (including chronic lymphocytic leukemia [CLL]; 45 percent), chronic myeloid leukemia (CML; 24 percent), or multiple myeloma (22 percent).
Patients under 65 years of age were over-represented in trials for lymphomas, CLL, CML, and multiple myeloma compared with the incidence of those cancers in this age group. For example, researchers found that nearly 80 percent of patients enrolled in trials for CML were under 65, but only half of patients diagnosed with CML are in this age group.
By contrast, patients aged 75 and older account for approximately 29 percent of CML diagnoses, yet this age group made up less than 4 percent of those enrolled in clinical trials to evaluate new treatments for the disease. They were also significantly underrepresented in trials of new treatments for lymphoma, CLL, and multiple myeloma compared with the incidence of each of these cancers in that age group.
"We weren't surprised to see that, overall, adults aged 75 years and older were under-represented in clinical trials, as this is common across cancer trials," said Dr. Kanapuru. "But we were surprised by the magnitude of the gap for this age group, particularly for CML trials."
The good news, she adds, is that among patients aged 65 to 74, data show the proportion enrolled in lymphoma (excluding CLL) and CML trials essentially mirrored the reported incidence of blood cancers in this age group. In multiple myeloma and CLL trials, the proportion enrolled in the 65-74-year-old age group was higher than the reported incidence in this group.
The FDA, through a number of guidance documents, actively encourages clinical trial sponsors to ensure that drug studies include the types of patients who will use the drug once it is approved. But Dr. Kanapuru points to multiple barriers to enrolling patients aged 75 and older in clinical trials. For example, patients with certain characteristics are regularly excluded from clinical trials for cancer treatments, including a history of previous cancers; less-than-optimal functioning of the heart, liver, kidneys, or other organs; or other co-existing illnesses. Many of these criteria serve to exclude older adults, who may be more likely than younger people to have co-existing illnesses or changes in organ function associated with aging. Social and financial factors can also play a role.
"In addition, doctors may hesitate to enroll these older patients because they aren't sure how they will tolerate investigational medications," Dr. Kanapuru said. "The 75-and-older population is also extremely heterogeneous. You can have one 75-year-old who is very healthy and another person of the same age who is frail and has a lot of co-existing illnesses."
Dr. Kanapuru stresses that it is important for clinicians to evaluate patients' suitability for enrollment in a clinical trial based on all of their characteristics and not to exclude them on the basis of age alone. Assessment tools that can help identify how older patients will fare and efforts to expand inclusion criteria are also needed, she says. Dr. Kanapuru also points out that the FDA has been vocal about the need to expand eligibility criteria and has engaged directly with sponsors and other stakeholders to examine ways to include specific populations of patients who are commonly excluded in cancer trials. She and her team believe these findings are a first step in raising awareness about the clear disparities in participation in blood cancer-related research studies, which are key to gathering evidence that ultimately informs treatment protocols.