‘Slow, Incremental Changes’ Are Increasing Participation of Older Adults in Clinical Trials

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Older adults continue to be proportionally underrepresented in oncology clinical trials, but the participation rate of adults aged 65 and older is increasing by “slow, incremental changes,” Stuart M. Lichtman, MD, FACP, FASCO, noted in an interview with The ASCO Post. Prompting those changes are the rapidly rising rate of cancer among older adults (expected to increase by 67% between 2010 and 20301), the realization that many older adults are willing and able to participate in clinical trials, calls by ASCO and other organizations to relax overly restrictive eligibility criteria for clinical trials, and the need for data on the pharmacokinetics of new and evolving cancer therapies in older adults.

As Dr. Lichtman remarked in a Kaiser Health News article, “It is difficult to practice evidence-based medicine in an older population because the data [aren’t] there.”2 Dr. Lichtman is a medical oncologist at Memorial Sloan Kettering Cancer Center, Commack, New York; Professor of Medicine at Weill Cornell Medical College, New York; and President of the International Society of Geriatric Oncology (SIOG).

Recent FDA Analysis

The U.S. Food and Drug Administration (FDA) recently analyzed enrollment of older adults in oncology clinical trials.3 The retrospective analysis compared cancer incidence data and demographic data for more than 231,000 patients enrolled in clinical trials supporting FDA approval of cancer therapies. Over a 10-year period, the cancer incidence rate for patients older than age 65 was 56%, but the rate of participation in clinical trials was 40%.

Doctors should be encouraged to think more about older patients and how to assess them. Tools are available online with great explanations….
— Stuart M. Lichtman, MD

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For those in the 65-to-69 and 70-to-74 age groups, there were small discrepancies between cancer incidence and clinical trial participation rates, but “for those over age 75, and especially over 80, you see a more striking underrepresentation of older adults,” the study’s lead author, Harpreet Singh, MD, Scientific Liaison with the FDA for Cancer in Older Adults, reported at the 2017 ASCO Annual Meeting.3 For those aged 75 to 79, the cancer incidence rate was 13%, and the clinical trial participation rate was 8%; for those older than age 80, the respective rates were 16% and 4%.

The clinical trial data are for the years 2005 to 2015, and the incidence rates come from the Surveillance, Epidemiology, and End Results (SEER) program data from 2010 to 2014. “The SEER data [are] reflective of new diagnoses, whereas the clinical trial data often represent patients who have had their cancer for several years, so the comparisons are not exact,” Dr. Singh acknowledged.

Differences by Cancer Sites

Analysis of data from approximately 176,000 patients with solid tumors showed that although older adults continued to be underrepresented in clinical trials for breast, colorectal, and lung cancers, older men were actually overrepresented in clinical trials for prostate cancer.

Prostate cancer bucks the trend. Younger patients are actually the ones who are underrepresented here.
— Harpreet Singh, MD

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Although 57% of new cases of breast cancer occurred in patients younger than age 65, 80% of those enrolled in FDA registration trials were under age 65. The rates for those between the ages of 65 and 74 “are more evenly matched,” Dr. Singh reported—23% of new cases vs 17% of clinical trial enrollees—but there was a “huge disparity in patients over 75, with only 4% of clinical trial participants over age 75, compared to 19% of new cases of breast cancer.”

For colorectal cancer, 57% of new cases occurred in those over age 65, but their clinical trial participation rate was 35%. “Those over 75 are severely underrepresented,” Dr. Singh said, accounting for 33% of new cases but only 8% of clinical trial participants.

“Lung cancer was one of our larger data sets, not surprising given the recent drug development in this tumor type,” Dr. Singh said. It is “very striking to see that while only 31% of new cases of lung cancer are diagnosed in those under 65, they make up 60% of clinical trial participants.” Once again, patients over age 75 “are severely underrepresented,” she added, with 37% of new cases but only 9% of clinical trial participants.

Bucking the Trend

“Prostate cancer bucks the trend,” Dr. Singh noted. “Younger patients are actually the ones who are underrepresented here,” with those under age 65 representing 43% of new cases but only 29% of clinical trial participants. Those aged 65 to 74 represent 38% of new cases but 43% of clinical trials participants. Those over age 75 make up 19% of new cases but 28% of clinical trial participants.

“It is unclear why this particular disparity exists, and I would be interested to hear different hypothesis or ways to go about further analyzing [these] data,” Dr. Singh said. “We continue to refine [these] data and expect to publish this in the form of a manuscript later this year,” she added.

Reevaluating Restrictive Criteria

Relaxing “overly restrictive eligibility criteria” for oncology clinical trials and encouraging clinicians to recruit older adults with cancer into clinical trials were key strategic elements in ASCO’s recommendations for improving the evidence base for treating older adults with cancer.4 “Given the rapidly aging population, this is a crucial time to act to ensure all patients with cancer receive high-quality, evidence-based care,” concluded the ASCO statement, issued in 2015. Dr. Lichtman, one of the authors of that statement, said ASCO is continuing the effort “to make eligibility less restrictive.”


Breast cancer
> 65 and < 74 years: 17%
> 75 years: 4%

Colorectal cancer
> 65 years: 35%
> 75 years: 8%

Lung cancer
> 75 years: 9%

Prostate cancer
> 65 and < 74 years: 43%
> 75 years: 28%

Source: Singh H, et al: 2017 ASCO Annual Meeting. Abstract 10009.

Other organizations also support less-restrictive criteria. The SIOG calls for extending phase II and III trials to patients with high levels of comorbidity or functional impairment, according to its research statement published online.5 In a recent article in the Journal of Geriatric Oncology, Dr. Singh and FDA colleagues wrote: “Eligibility criteria must be closely examined so as not to exclude patients who would be considered vulnerable or ‘frail’…. Older adults should be enrolled in clinical trials if they are stable, can be safely and ethically enrolled, and are willing to participate. Efforts are underway to encourage sponsors to take a more rational approach to eligibility criteria for clinical trials and include the potential to relax certain laboratory requirements that encompass multiple organ functions if safety is not compromised.”6

The FDA Oncology Center of Excellence and ASCO “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,” according to an article by Dr. Singh and others in the ASCO Daily News,7 published during the 2017 ASCO Annual Meeting. A primary goal of the workshop “is to address the ASCO recommendations to improve the evidence base for treating older adults with cancer,” the authors stated.

More Pertinent Endpoints

“Available clinical trials often do not include endpoints pertinent to the older adult population, such as preservation of function, cognition, and independence,” according to a 2014 article in the Journal of Clinical Oncology by the Cancer and Aging Research Group.8 Identifying novel endpoints could be important for identifying treatment options for patients traditionally excluded from clinical trials, the report noted.

Dr. Lichtman said that endpoints such as maintenance of function and independence, time without symptoms, and overall quality of life are appropriate for clinical trials in older adults, but he doesn’t see much progress toward including these endpoints. “You need the FDA and other organizations to really push it and give sponsors a motivation for doing it,” Dr. Lichtman remarked.

Understanding Older Patients Better

As a strategy to improve cancer care in older adults, the authors of the FDA analysis also suggested “incorporating elements from geriatric assessment tools.” This would provide “baseline information to try to understand the patients better,” Dr. Lichtman said, “such as simple activities of daily living, falls, general health. That kind of information that will help gather data for future use,” is needed, he added, because appropriate use of cancer therapies in older patients “is still a work in progress.”

Geriatric assessment tools also have been shown in studies “to be predictive of adverse events. There is value to collecting that information. How to incorporate it into general practice is an ongoing issue that people are exploring,” Dr. Lichtman stated.

“In general, doctors should be encouraged to learn more and think more about older patients and how to assess them. Tools are available online with great explanations, so that information is not difficult to obtain,” Dr. Lichtman said.

While Awaiting Clinical Trial Data

What data can physicians rely on in the absence of robust data from clinical trials with fair representation of older adults? “We are always extrapolating from clinical trial data in general, and for older patients in particular, it is even more important,” Dr. Lichtman said. “It is also more difficult because not many 80-year olds have been on clinical trials. We have to be cautious and careful about getting the data but understand the patients we are seeing were not represented on trials, so good clinical judgment and extrapolation are always going to be necessary.”

Adverse effects may differ in older vs younger patients. “It is well known that neuropathy is worse” in older adults, Dr. Lichtman pointed out. “Interestingly, immunotherapy may not be worse in older people” in terms of adverse effects, he said, “but that kind of data is being accumulated.”

Randomized studies are preferable, but observational studies and data-mining are also yielding information about efficacy and adverse effects of cancer therapies in older adults, “which wouldn’t be otherwise available,” Dr. Lichtman added.

More Data in the Coming Months

“We need to provide as much data as possible so clinicians can make informed decisions,” Dr. Singh said in her presentation. Summaries for cancer drugs recently approved by the FDA are online, “as well as top-line demographic data on our clinical trial snapshots page.” In addition, the Oncology Center of Excellence has initiated a patient-focused drug development program, with one goal: to identify rigorous methods to capture, analyze, and present information on patient-reported symptoms, function, and other aspects of health-related quality of life. “We are actively pursuing international collaboration to identify standard methods to analyze and present these data and are looking for opportunities to incorporate informative patient-reported outcome data in clinical and statistical reviews as well as published FDA approval summaries,” Dr. Singh advised.

“In the postmarketing setting, drugs can be studied in older and more diverse patients to gather more information, either by industry or cooperative groups or even in collaboration,” Dr. Singh added. “I do believe we should use real-world data not as a substitute for clinical trial data but to help further inform us on the uptake, safety, and efficacy of these new drugs. There are several groups looking at [these] data, including ASCO’s CancerLinQ™.” ■

DISCLOSURE: Drs. Lichtman and Singh reported no conflicts of interest.


1. Smith BD, Smith GL, Hurria A, et al: Future of cancer incidence in the United States: Burdens upon an aging, changing nation. J Clin Oncol 27:2758-2765, 2009.

2. Graham J: Seniors miss out on clinical trials. Kaiser Health News, June 29, 2017. Available at Accessed July 25, 2017.

3. 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. 2017 ASCO Annual Meeting. Abstract 10009. Presented June 5, 2017.

4. Hurria A, Levit LA, Dale W, et al: Improving the evidence base for treating older adults with cancer: American Society of Clinical Oncology statement. J Clin Oncol 33:3826-3833, 2015.

5. International Society of Geriatric Oncology: Research statement. Available at Accessed July 25, 2017.

6. Singh H, Beaver JA, Kim G, et al: Enrollment of older adults on oncology trials: An FDA perspective. J Geriatr Oncol 8:149-150, 2017.

7. Singh H, Levit L, Hurria A: Progress through collaboration: ASCO and FDA’s efforts to improve the evidence base for treating older adults with cancer. ASCO Daily News. 2017 ASCO Annual Meeting, June 4, 2017.

8. Hurria A, Dale W, Mooney M, et al: Designing therapeutic clinical trials for older and frail adults with cancer: U13 conference recommendations. J Clin Oncol 32:2587-2594, 2014.

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