Eliminating inequities in health care is an important priority. One persistent inequity involves the lack of data to guide cancer care for older adults. Although clinical trials provide the strongest foundation for acquiring such data, a recent analysis by the Food and Drug Administration (FDA) found that only 24% of patients enrolled in trials supporting oncology-drug approvals were 70 years of age or older, as compared with the 42% of such patients in the Surveillance, Epidemiology, and End Results database who would be eligible to receive the treatments after they were approved.1 Most trials also had exclusion criteria preventing all but the fittest older adults from participating. Roughly one in four patients with the most common cancers is older than 75. This growing population has missed out on care improvements that could stem from clinical research, a concern that was discussed at a National Academies of Sciences, Engineering, and Medicine workshop that was convened to discuss this topic in January 2021.
The proportion of U.S. residents who are elderly is steadily increasing; in 2019, roughly 13 million Americans were at least 80 years of age. Older patients with cancer are a heterogeneous group, and for several reasons, the results of studies conducted in younger patients may not be generalizable to this population. As compared with the average patient, older or frail adults may tolerate certain treatments less well, may derive less benefit from treatments, or may have different treatment goals — for example, they may value quality of life more than duration of survival. The prevalence of coexisting conditions such as cardiopulmonary disease, diabetes, arthritis, sarcopenia, and depression increases with age; Medicare data indicate that 40% of older adults with cancer have at least one other chronic condition, and 15% have two or more additional conditions.2 The cumulative effects of coexisting conditions and their associated therapies can negatively influence cancer treatment and prognosis.
Improving care for older adults requires understanding the effects on cancer treatment of the normal aging process, social determinants of health (such as neighborhood and education status), and coexisting conditions. Because there are insufficient data on these relationships, older patients with cancer and their physicians must make life-altering decisions without adequate, evidence-based guidance. Such decisions may also be influenced by clinician or caregiver bias, which can harm older patients or limit their treatment options. Age discrimination, unconscious or otherwise, is an important concern — clinicians and caregivers may assume, without justification, that older adults won’t tolerate or won’t benefit from certain treatments. Age discrimination may also help explain the disproportionately low rates of participation in clinical trials among older adults. A study using data from the National Cancer Institute (NCI) National Clinical Trials Network found that physicians discussed trial participation with 76% of eligible patients younger than 65 years of age, as compared with only 58% of those 65 or older. When it came to older patients, 11% of physicians identified age as a reason they didn’t enroll a patient in a trial.3
Previous calls to action on this topic have gone unanswered. A 2013 report by the Institute of Medicine (now the National Academy of Medicine), Delivering High-Quality Cancer Care, found that older adults were underrepresented in clinical research and called for increased data collection. The report emphasized the importance of capturing detailed functional data with tools such as comprehensive geriatric assessments, which address cognition, emotional state, communication capacity, strength, mobility, nutritional status, and other variables.4 The American Society of Clinical Oncology (ASCO) then published its own recommendations, and a series of workshops sponsored by the FDA, the NCI, Friends of Cancer Research, the National Institute on Aging, and ASCO called for the people and entities designing, funding, and conducting clinical research to address knowledge gaps related to the treatment of older adults. Despite these recommendations, there has been little recent progress in this area. To move forward, we believe it’s necessary to address the disincentives and biases that contribute to this inequity.
Patients often choose to participate in a clinical trial because of a physician’s recommendation. One reason physicians are less likely to suggest trial enrollment to older patients than to younger ones3 may be that substantially more effort is required to ensure that older adults, particularly those with cognitive decline or mobility problems, meet the requirements for participation. It’s also possible that negative stereotypes, whether overt or unconscious, lead clinicians to assume that older patients won’t want to participate, are at increased risk for adverse effects, or are less likely than younger patients to benefit from treatment.
In addition, clinical trials are rarely designed with older adults in mind, and because conducting trials is generally challenging and expensive, components that increase complexity or delay accrual are discouraged unless they are specifically required or justified by additional funding. Finally, study sponsors may face disincentives for recruiting older adults. Trials that are conducted to justify regulatory approval of a new treatment often exclude patients with certain coexisting conditions because of concerns about toxic effects (even if the benefits associated with a therapy are expected to justify any risks), and quality-of-life–related end points that tend to be valued by older patients are rarely used to support drug approvals.
The geriatric oncology community has developed study designs, physiological fitness assessments, and end points that can be used to generate high-quality data on the benefits and risks associated with cancer treatments among older patients (see ). Some progress has been made for cancers that disproportionately affect older adults, such as acute myeloid leukemia and non–small-cell lung cancers with mesenchymal–epithelial transition exon 14 (METex14) skipping alterations. Moreover, trials in patients with metastatic breast cancer and advanced pancreatic cancer have shown that it’s possible to conduct studies in older adults.5 These studies addressed common concerns of older patients, for instance by determining minimum effective drug doses, assessing treatment tolerance among patients with organ dysfunction, or including quality-of-life–related end points. Such studies remain rare, however, because pharmaceutical sponsors aren’t required to collect data that are relevant to older adults. Relying on support from the National Institutes of Health to deliver these data is insufficient because of the many competing priorities for public funding in the area of cancer clinical research.
The FDA (where one of us works) has long expressed concern about the lack of evidence to guide care throughout the life span. In 2020, the agency issued a draft guidance for oncology-drug manufacturers that stated “Geriatric (i.e., older adult) use information must be included in labeling, unless clearly inapplicable,” while acknowledging that such information is rarely included because of limited data availability.
Recent experience demonstrates, however, that guidance without accountability for progress is unlikely to be sufficient. Despite numerous efforts, the persistent underrepresentation of older adults in cancer clinical trials has resulted in an inadequate evidence base that threatens the delivery of high-quality, patient-centered care. We believe that ensuring that older adults are included in research throughout the drug-development continuum is an ethical imperative. Clinical trials could also collect data on quality of life, and manuscripts should report the number of participants in various age groups and demonstrate that the age distribution of participants is similar to that of patients with the type of cancer under study.
The FDA could exert the maximum influence allowed to require submission of data related to the treatment of older adults, particularly when older or frail patients account for a substantial proportion of people with a given disease. For diseases that are common in older people, sponsors could perform stratified analyses to understand a drug’s benefits and risks in these populations. The FDA could also consider outlining postmarketing commitments for sponsors when data from registration trials don’t sufficiently address a drug’s safety and efficacy in older adults. Congress would need to authorize the FDA to enforce some of these guidelines and policies. We believe these measures would represent important progress toward promoting equity for older adults with cancer.
References (5)
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Singh H, Kanapuru B, Smith C, et al. FDA analysis of enrollment of older adults in clinical trials for cancer drug registration: a 10-year experience by the U.S. Food and Drug Administration. J Clin Oncol 2017;35:Suppl 15:10009-10009
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Sarfati D, Koczwara B, Jackson C. The impact of comorbidity on cancer and its treatment. CA Cancer J Clin 2016;66:337-350
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Javid SH, Unger JM, Gralow JR, et al. A prospective analysis of the influence of older age on physician and patient decision-making when considering enrollment in breast cancer clinical trials (SWOG S0316). Oncologist 2012;17:1180-1190
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Institute of Medicine. Delivering high-quality cancer care: charting a new course for a system in crisis. Washington, DC: National Academies Press, 2013
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Muss HB, Berry DA, Cirrincione CT, et al. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med 2009;360:2055-2065.
