Statistically, people over 65 have a greater chance of a cancer diagnosis. We know that cancer is a disease associated with aging, yet limited clinical data exists for older adults. Multiple studies have found that people age 65 and older are underrepresented in both cancer registration trials and the National Cancer Institute’s clinical trials.
A 2017 study by the American Association for Cancer Research found that patients age 65 and older represented only 36 percent of the patients enrolled in clinical trials. The study analyzed data from all the cancer trials reported as completed between 2003 to 2016 in clinicaltrials.gov, a database of publicly and privately supported clinical trials. Since the elderly are underrepresented in trials, they will also be underrepresented for the types of cancers that disproportionately affect them.
Most of what we know about cancer therapeutics is based on clinical trials in younger patients. As a result, there is considerable lack of knowledge of the risks and benefits of cancer treatments in older adults, especially those over age 70. We know that elderly patients are more likely to suffer severe side effects from their cancer treatments and recover from them more slowly.
In 2017, an oncology workshop was held between the US Food and Drug Administration and the American Society of Clinical Oncology (ASCO), to look at aspects of clinical trial design and clinical trial recruitment and strategies in order to facilitate a change in culture and way of thinking that might encourage more elderly patients to enroll in clinical trials.
...there is considerable lack of knowledge of the risks and benefits of cancer treatments in older adults, especially those over age 70.
The meeting was divided into four sessions, designing clinical trials for older patients, increasing enrollments to FDA registration trials, leveraging real world evidence, and lessons learned from pediatrics payers and the European Medical Association.
The consensus was that we need standards of care for those who are vulnerable, frail, and those who have multiple chronic conditions, specifically for those over age 75. And, we need comparative effectiveness studies.
Focus was given to study examples that were designed for older adults. The first example was a study where inclusion criteria were defined by vulnerability. This was a study looking at patients with chronic lymphocytic leukemia and that only enrolled patients with coexisting conditions. The study design was able to provide a new standard of care for patients with coexisting conditions, those that are most likely to be seen in clinics.
The second study tested the utility of treatment allocation by geriatric assessment (geriatric assessment versus usual care) and demonstrated that studies designed to address complexity can be done efficiently and effectively in an older adult population. Examples of novel trials designed to intentionally include elderly patients were via extension or parallel cohort and with elderly patients with comorbidities.
Efforts are underway to encourage sponsors to take a more rational approach to eligibility criteria for clinical trials, including relaxing requirements based on multiple organ functions if safety is not compromised. A recent perspective article provided valuable insight into FDA’s thoughts on the enrollment of older adults in oncology trials. Modernizing and relaxing eligibility criteria based on renal function, cardiac function and prior concurrent malignancy. These are some important recommendations for clinical trial protocols going forward, particularly with respect to renal function.
If there is no good scientific reason for using a creatinine clearance of 60, which is the gold standard that almost no one can achieve, it should be 30. That change alone is expected to have substantial impact, in addition to making adjustments with respect to cardiac function and prior and concurrent malignancies with window decreased to two years if it does not interfere with study end points data and concurrent malignancies are acceptable if not requiring current therapy.
(For most clinical trials there are exclusion criteria stating that patients with previous malignancies will be excluded/ not allowed to be enrolled in the study if having a history of cancer, including hematologic malignancy and solid tumors, within 10 or five years before screening. For elderly population more relaxant criteria was considered to have this period decreased to two years.)
Having an elderly patient on a study could put it at risk for more severe AE / SAEs and potentially more protocol deviations (due to comorbidities, impaired social support, cognitive and functional impairment) which could then impact adherence to protocol requirements and present a financial burden. The opportunity for systematic change requires involved sponsors of all types to implement modernize eligibility criteria recommendations.
This systematic change is possible by translating ASCO's recommendations into action and by continuing to increase advocacy. In partnership with the NIH and the FDA, ASCO can facilitate development integration of core measures and geriatric measures in clinical trials.
It is encouraging to see that efforts are ongoing to improve the evidence base for older adults with cancer. Rapid closure of the evidence gap will require continued multi stakeholder engagement and a change in culture. By taking these steps we can ensure that all patients with cancer receive high quality, evidenced-based and personalized care.
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