- Older adults are a growing segment of our oncology population but remain underrepresented in clinical trials.
- ASCO and the FDA are both working to improve clinical trial participation among older adults with cancer to improve care.
- A planned FDA/ASCO public workshop on Cancer in Older Adults will address ASCO’s recommendations to improve the evidence base for treating older adults with cancer.
Older adults are a growing segment of our oncology population. Cancer incidence is projected to increase 67% in people age 65 and older between 2010–2030.1 However, multiple studies have found that people age 65 and older are underrepresented in both cancer registration trials and the National Cancer Institute’s National Clinical Trials Network (NCTN) clinical trials, with only modest improvement over time.2 Thus, most of what we know about cancer therapeutics is based on clinical trials conducted in younger patients, and oncology providers lack robust knowledge of the risks and benefits of cancer treatments in older adults, especially those over age 70.
ASCO and the U.S. Food and Drug Administration’s (FDA’s) Office of Hematology and Oncology Products are co-hosting a public workshop on Cancer in Older Adults at FDA’s headquarters this fall. The meeting will convene a diverse group of stakeholders responsible for the treatment and monitoring of geriatric patients in oncology. Both organizations have previously undertaken projects designed to increase enrollment of older adults on clinical trials.
Evolution of Guidance
The FDA published its first Guidance for Industry on this topic in 1989, encouraging sponsors to study new drugs in the full range of patients who are likely to be treated, including those older than age 70.3 In 2012, the FDA published an updated Guidance for Industry, E7 Studies in Support of Special Populations: Geriatrics in response to sponsors’ questions regarding the previous guidance. The 2012 document includes a thorough discussion of broadening eligibility criteria, as well as other considerations in trial design to facilitate the enrollment of older adults.4
In a separate effort, the 2013 Institute of Medicine (IOM) report Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis concluded that the lack of evidence in older adults undermines the quality of cancer care.5 It also highlighted the potential dangers of the projected shortage of health care providers with expertise in geriatrics. The IOM report made two recommendations to improve our evidence base and strengthen the national workforce that cares for older patients with cancer: (1) increase the breadth of collected data by matching the characteristics of the study population to those of patients with the disease (i.e., enroll more patients over age 70 onto clinical trials), and (2) increase the depth of collected data by capturing a more detailed characterization of the study population through evaluation tools, such as a comprehensive geriatric assessment.
Although the IOM’s recommendations brought national attention to a pressing public health issue, it did not take steps to implement those recommendations. As a result, ASCO formed a working group of 11 individuals with expertise in geriatric oncology to review the IOM report and to identify actionable strategies for improving research on older adults with cancer. After substantial deliberations and approval from ASCO’s Cancer Research Committee and Board Executive Committee, the ASCO working group in 2015 published the article “Improving the Evidence Base for Treating Older Adults with Cancer: American Society for Clinical Oncology Statement.”6
The ASCO statement makes five overarching recommendations that address key strategies to improve the evidence base for the treatment of older adults with cancer through advocacy, research, and education. Each recommendation includes a list of specific action items. The recommendations include:
- Increase the FDA’s authority to incentivize and require research in older adults with cancer.
- Use clinical trials to improve the evidence base for treating older adults with cancer.
- Leverage the full range of research designs and infrastructure for generating evidence in older adults with cancer.
- Increase clinicians’ recruitment of older adults with cancer to clinical trials.
- Use journal policies to improve researchers’ reporting on the age distribution and health-risk profiles of research participants.
The first recommendation includes policy and/or legal changes to the FDA’s authority to require and incentivize clinical trials that include older adults, which can be achieved through the engagement of the multiple stakeholders involved in clinical cancer research. ASCO continues to advocate for these changes and to educate policymakers on their importance and the need for geriatric oncology.
Recommendations two, three, and four speak to the need for increased research to guide evidence-based care of older adults. Aging is a heterogeneous process and many older adults are able and willing to participate in clinical trials. The FDA’s 2012 guidance suggested that geriatric patients with comorbidities or those who are taking concomitant therapies should not be automatically excluded from trials because including such patients provides data that may detect drug–drug interactions. The guidance recommends that sponsors closely examine eligibility criteria so as to not inadvertently exclude older adults.
In addition, ASCO and Friends of Cancer Research have launched a collaborative effort involving more than 40 stakeholders from across the cancer research community, including patient advocates, clinical investigators, drug and biotech manufacturers, pharmacologists, and medical reviewers from the FDA, to modernize eligibility criteria. 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.7 A recent perspective article provided valuable insight into FDA’s thoughts on the enrollment of older adults on oncology trials.8
Drug sponsors and the NCTN are required to devise strategies to recruit patients that are reflective of their intended population. Several publications in the Journal of Clinical Oncology provide recommendations on designing clinical trials in older adults with cancer.9,10 The FDA’s frequent communication with sponsors during the drug development process provides opportunities to discuss the age demographics of their target population early in the development of clinical trials. In breast cancer, for example, up to 19.7% of patients are older than age 75. Thus, a development program for a breast cancer drug should aim to enroll a representative population of older adults. The FDA could also consider providing more detailed labeling information on the clinical experiences with older adults as further encouragement for sponsors to include a representative cohort of patients on clinical trials.
A key component of clinical trials in older adults is the inclusion of a geriatric assessment, which provides clinicians with information on the heterogeneity of the aging process beyond chronologic age. Incorporating elements from geriatric assessment tools, such as functional status, cognitive function, and a thorough assessment of comorbid conditions, may help identify older adults most likely to benefit from treatment.
The geriatric assessment also captures components of patient preference, which is particularly important in older patients with cancer. A disease-centered approach may neglect key elements such as a patient’s willingness to tolerate effects of therapy, which may lead to loss of independence. The patient perspective is gaining an increasingly important role in clinical trial design and may also have implications for more informed labeling. The FDA encourages incorporating these elements into clinical trial design and collecting patient data prospectively, which may better inform patient selection for registration trials.
ASCO recommendation five leverages information collected in ongoing research studies through improved reporting of clinical trials in medical journals on the age distribution and health-risk profiles of research participants and age-related data analyses. The FDA is also updating its current thinking about standardized age categories (e.g., grouping older adults in more discrete categories for analysis such as ages 65-74 or 75-84, rather than “younger than age 65”).
In response to public feedback and in an effort to be more transparent, the FDA launched Drug Trials Snapshots, which outlines the participation of people in clinical trials by sex, race, and age. This information is publicly available on the FDA’s website.11 Providing more detailed information on the age distribution and characteristics of clinical trial participants could inform clinicians about important age-related efficacy, safety, and dosing considerations.
A primary goal of the planned FDA/ASCO public workshop on Cancer in Older Adults is to address the ASCO recommendations to improve the evidence base for treating older adults with cancer. We look forward to this major milestone in the path toward ensuring that our older patients with cancer have access to evidence-based care. Together with investigators, advocates, government, industry, and research institutions, we can fill the knowledge gap needed to improve the care of our rapidly growing population of older adults with cancer.
About the Authors: Dr. Singh is a scientific liaison for Cancer in Older Adults with the U.S. Food and Drug Administration. Ms. Levit is an associate director in the Center for Research & Analytics (CENTRA) at ASCO. Dr. Hurria is the director of the Cancer and Aging Research Program at City of Hope.