n old idea — using the body’s immune system to fight cancer cells, first proposed more than a century ago — has become one of the most promising approaches to treating cancer today. Immunotherapy is effective against a variety of cancers, with sometimes spectacular results. But I worry about how effective it is in people over age 65, who make up half of cancer patients.
We know that immunotherapy is tolerated by older individuals. But how well they respond to it and the side effects it causes them may be different from those observed in most clinical studies for two reasons. One is that clinical trials tend to include younger participants. The other is because of an aging process known as immunosenescence. It causes the immune system to change and become less effective over time. Since immunotherapy involves harnessing the immune system to fight cancer, there are questions about how well it works in patients whose immune systems are changing.
Since the first immunotherapy for cancer, ipilimumab (Yervoy), was approved in 2011, this approach has begun to transform cancer care. Today, immunotherapy is used to treat a number of cancers, from glioblastoma to advanced melanoma and lung cancer. According to the Cancer Research Institute, six types of immunotherapy clinical trials are taking aim at leukemia. It may also have the potential to help patients with breast cancer.
But we don’t know as much as we should about immunotherapy for older individuals as they are poorly represented in clinical trials. In 2013, individuals between the ages of 65 and 69 years made up 17 percent of clinical trial participants, those between the ages of 75 and 79 years made up 8 percent, and those who were 80 years and older made up only 4 percent.
Given that immunosenescence may change patients’ responses to drug therapies, we can’t predict responses to it among older individuals based on studies that included only non-geriatric populations.
Immune checkpoint inhibitors, such as pembrolizumab (Keytruda) or nivolumab (Opdivo), tend to be better tolerated than traditional chemotherapy drugs. Yet few clinical trials have examined their toxicity in older populations. In one study of these drugs, adverse events ranging from severe but not life-threatening to life-threatening or resulting in death were recorded more often in patients aged 70 years and older than among those younger than 65.
To help everyone — physicians, researchers, and patients — better understand how the immune system changes with age and how those changes could influence the success of immunotherapy, future studies must include a more representative elderly population, including those with multiple health issues.
That will require a concerted effort on multiple fronts. First and foremost, we need to educate elderly patients about the value of taking part in clinical trials, especially those related to immunotherapy. In general, the medical community should be more aware and flexible when defining who can participate in clinical trials by not setting upper age limits or excluding older individuals without valid reasons. This will ensure better representation of the population that is actually receiving cancer treatment in the real world without compromising results. Oncologists also have a duty to tell their patients about clinical trials earlier in their treatment process to offer them potentially better options for managing their cancer. Many doctors think of clinical trials when it’s too late and a patient’s health isn’t good enough to enroll in a trial.
More traditional barriers also prevent some elderly individuals from taking part in clinical trials. One is their limited physical and cognitive reserves, which can make trial participation and extra visits to the hospital a burden. In addition, some patients have difficulty understanding written information or information provided over the phone. Finding ways to overcome these barriers may help increase the number of older patients in trials.
By 2040, patients older than 65 will account for more than 70 percent of all new cancer diagnoses. That means there is no time like the present to ensure that the most promising cancer treatments are safe for, and available to, the majority of people who will need them.
As we age, our immune systems change, presenting us with new challenges. Access to promising, life-extending cancer treatments like immunotherapy should not be among these challenges simply because older patients have not been included in clinical trials.
Ankur R. Parikh, D.O., is the medical director of precision medicine at Cancer Treatment Centers of America and a consultant for Foundation Medicine Inc. This commentary is adapted from a longer article published in Oncology Times.