Should there be more elderly-specific clinical trials?

POINT

Corey J. Langer, MD

Elderly-specific trials are especially needed for the ‘oldest old,’ those aged 80 and older.

There should be more elderly-specific clinical trials, but the elderly should also be encouraged to participate in trials that are not age specific. We probably have more than enough retrospective data on elderly patients who are fit, at least in the context of advanced NSCLC. These data indicate that the elderly can do as well or nearly as well on the same treatment regimens that are used in younger patients.

There are a number of caveats, however. Clinical trials that are not age specific have less emphasis on comorbidity analyses and supportive approaches, which become more and more important as patients age.

Secondly, patients older than 70, and especially those older than 80, are woefully under-represented in clinical trials, Even though an increasing number of patients we see are elderly. In that respect, we need elderly-specific trials to focus particularly on the “oldest old.” I would argue that a 71-year-old patient who is fit and active can comfortably participate in any trial. For 80-year-old patients, however, even if they appear fit, I would have concerns about enrolling this cohort into clinical trials.

Elderly-specific trials are more common in Europe, where age is often used as a cutoff for clinical trial enrollment. In fact, a landmark study in elderly patients with advanced lung cancer, the ELVIS study, was conducted in Italy. This was the first elderly-specific trial in advanced NSCLC to show a survival advantage for elderly patients receiving chemotherapy vs. best supportive care. Since then, there have been a number of elderly-specific trials, randomized phase-3 trials, almost all conducted in Europe and Japan.

Despite this, there are still major holes. For example, we have not yet looked at pharmacokinetics in the elderly with lung cancer or at how to optimize proper dose adjustments. Most importantly, we have yet to conduct an elderly-specific trial substantiating the role of platinum, which is a standard component of the therapeutic platform in NSCLC.

In the United States, when it comes to most therapeutic clinical trials, we do not discriminate on the basis of age. This “benefit” is also our bane. Our current trials do not generally use age as an exclusion criterion, but conversely, it is more difficult to design and launch a trial that is age specific.

This is an issue that will never go away. The population in the United States and around the world is aging. Patients aged 75 to 80 and older are one of the fastest-growing cohorts. Most of our data are extrapolated from clinical trials in which there were no or very few elderly patients enrolled. Clinical trials in general need to be publicized more through patient advocacy groups and presented as options to patients. There should also be more partnerships with the NCI and the industry to facilitate the conduct of these trials.

Corey J. Langer, MD, is a Professor of Internal Medicine and Director of the Thoracic Oncology Program at the Abramson Cancer Center of the University of Pennsylvania in Philadelphia.

COUNTER

Harvey Jay Cohen, MD

Elderly-specific trials can help answer questions unique to older patients.

There are many trials that can be done that are not age specific, but we need elderly-specific trials for a few reasons. One is that there are particular questions that are unique to an older patient with cancer. Trials looking at the use of geriatric assessments as a tool for the care of older patients or trials looking at the pharmacokinetics of a drug in older patients need to be done specifically in older people.

The big issue is that when trials are done across a spectrum of ages, the trials tend to complete accrual, and there are many more younger patients than there are older patients. There are often never enough older patients to learn anything specific. Some people may say that age-specific trials are not necessary because there are no age restrictions on clinical trials. This may be true, but what almost always happens is that the bulk of the patients are much younger.

There are two possible ways to address this. Age-specific trials are one option. Another option is to have a mandated number of people from the various age cohorts enrolled into a trial with no age restrictions.

In a trial that is truly not age specific, the treatment is going to be tolerable for both younger and older people. But one is going to have more trouble delivering many drug regimens, such as aggressive treatment for acute leukemia, to an older group of patients. In that case, trials looking specifically at regimens designed for an older group would be more logical. One may want to design a regimen that is tailored to an older cohort, taking into account things like multiple comorbidities.

That raises another issue. Most of our trials that are not age specific have strict inclusion criteria, and many patients in the older age group are excluded because of comorbidities. Unless we design trials with that in mind, we are never going to be able to treat these people. If you want to treat patients in the real world, you have to be willing to treat similar patients in the trials.

Harvey Jay Cohen, MD, is Professor and Chair of Medicine, and Director of the Center for the Study of Aging and Human Development at Duke University.

POINT

Corey J. Langer, MD

Elderly-specific trials are especially needed for the ‘oldest old,’ those aged 80 and older.

There should be more elderly-specific clinical trials, but the elderly should also be encouraged to participate in trials that are not age specific. We probably have more than enough retrospective data on elderly patients who are fit, at least in the context of advanced NSCLC. These data indicate that the elderly can do as well or nearly as well on the same treatment regimens that are used in younger patients.

There are a number of caveats, however. Clinical trials that are not age specific have less emphasis on comorbidity analyses and supportive approaches, which become more and more important as patients age.

Secondly, patients older than 70, and especially those older than 80, are woefully under-represented in clinical trials, Even though an increasing number of patients we see are elderly. In that respect, we need elderly-specific trials to focus particularly on the “oldest old.” I would argue that a 71-year-old patient who is fit and active can comfortably participate in any trial. For 80-year-old patients, however, even if they appear fit, I would have concerns about enrolling this cohort into clinical trials.

Elderly-specific trials are more common in Europe, where age is often used as a cutoff for clinical trial enrollment. In fact, a landmark study in elderly patients with advanced lung cancer, the ELVIS study, was conducted in Italy. This was the first elderly-specific trial in advanced NSCLC to show a survival advantage for elderly patients receiving chemotherapy vs. best supportive care. Since then, there have been a number of elderly-specific trials, randomized phase-3 trials, almost all conducted in Europe and Japan.

Despite this, there are still major holes. For example, we have not yet looked at pharmacokinetics in the elderly with lung cancer or at how to optimize proper dose adjustments. Most importantly, we have yet to conduct an elderly-specific trial substantiating the role of platinum, which is a standard component of the therapeutic platform in NSCLC.

In the United States, when it comes to most therapeutic clinical trials, we do not discriminate on the basis of age. This “benefit” is also our bane. Our current trials do not generally use age as an exclusion criterion, but conversely, it is more difficult to design and launch a trial that is age specific.

This is an issue that will never go away. The population in the United States and around the world is aging. Patients aged 75 to 80 and older are one of the fastest-growing cohorts. Most of our data are extrapolated from clinical trials in which there were no or very few elderly patients enrolled. Clinical trials in general need to be publicized more through patient advocacy groups and presented as options to patients. There should also be more partnerships with the NCI and the industry to facilitate the conduct of these trials.

Corey J. Langer, MD, is a Professor of Internal Medicine and Director of the Thoracic Oncology Program at the Abramson Cancer Center of the University of Pennsylvania in Philadelphia.

COUNTER

Harvey Jay Cohen, MD

Elderly-specific trials can help answer questions unique to older patients.

There are many trials that can be done that are not age specific, but we need elderly-specific trials for a few reasons. One is that there are particular questions that are unique to an older patient with cancer. Trials looking at the use of geriatric assessments as a tool for the care of older patients or trials looking at the pharmacokinetics of a drug in older patients need to be done specifically in older people.

The big issue is that when trials are done across a spectrum of ages, the trials tend to complete accrual, and there are many more younger patients than there are older patients. There are often never enough older patients to learn anything specific. Some people may say that age-specific trials are not necessary because there are no age restrictions on clinical trials. This may be true, but what almost always happens is that the bulk of the patients are much younger.

There are two possible ways to address this. Age-specific trials are one option. Another option is to have a mandated number of people from the various age cohorts enrolled into a trial with no age restrictions.

In a trial that is truly not age specific, the treatment is going to be tolerable for both younger and older people. But one is going to have more trouble delivering many drug regimens, such as aggressive treatment for acute leukemia, to an older group of patients. In that case, trials looking specifically at regimens designed for an older group would be more logical. One may want to design a regimen that is tailored to an older cohort, taking into account things like multiple comorbidities.

That raises another issue. Most of our trials that are not age specific have strict inclusion criteria, and many patients in the older age group are excluded because of comorbidities. Unless we design trials with that in mind, we are never going to be able to treat these people. If you want to treat patients in the real world, you have to be willing to treat similar patients in the trials.

Harvey Jay Cohen, MD, is Professor and Chair of Medicine, and Director of the Center for the Study of Aging and Human Development at Duke University.