Immunotherapy may help elderly cancer patients, but…

c Cancer risks increase dramatically as we age. More than half of all new cancers are diagnosed in patients 65 or older, and more than 25 percent of new cases are in patients 75 or older, according to the National Cancer Institute. Therefore, it is reasonable to conclude that checkpoint inhibitors, a growing class of immunotherapy drugs approved to treat various types of cancer in patients of all ages, may also be a strong option for elderly patients. But that may not always be the case, says Ankur Parikh, MD, medical director of precision medicine at Cancer Treatment Centers of America. ^® (CTCA) and a hematologist, oncologist, and medical oncologist at our Philadelphia Hospital.

Percentage of new cancer cases by age

Elderly patients, 65 years of age or older, and those with compromised immune systems may not have the robust response to immunotherapy that some younger patients experience. Because older patients are less likely to participate in clinical trials, less clinical data is available about why they may or may not respond to these treatments. “Immunotherapy certainly helps many patients, and we’re seeing very interesting responses in certain populations,” says Dr. Barrick. “What we do know is that patients’ immune system changes and develops over time. As people age, the immune system changes too. And would a 65-year-old respond to immunotherapy in the same way as someone under 40? This question has not yet been answered. , and unfortunately, there is not a large elderly population in many clinical trials. So we don’t get these answers often.”

Cancer risks increase with age for many reasons.

• Cell replication errors occur more frequently in the elderly, which increases the chances of producing a DNA mutation that can lead to cancer. A 2017 study by researchers at Johns Hopkins University School of Medicine concluded that errors that occur when cells constantly divide could be responsible for more than 60 percent of all cancers.
• Years of habits like drinking, smoking and poor diet are taking their toll. A 2016 Harvard study of nearly 130,000 Americans found that the risk of cancer can be reduced by up to 40 percent by adopting a healthy lifestyle.
• Exposure to carcinogens and environmental risk factors, such as asbestos, secondhand smoke, pesticides, and ultraviolet rays from the sun also increase the risk.

When we are younger, our cells have repair mechanisms that often correct DNA mutations caused by errors of transcription or exposure. And when they don’t fix it, the immune system will likely start attacking and killing the faulty cells. But as we age, our repair mechanisms begin to fail and our immune systems weaken, which can allow defective cells to grow out of control and form a tumor. I think the challenge for elderly patients is that their immune systems may not be nearly as efficient, or they may suffer from something called immune aging. Senescent cells, which have not died but can no longer grow or divide, sometimes have precancerous properties. Other senescent cells, including immune cells, can exist in a zombie-like state: alive, but not working properly. Checkpoint inhibitors, designed to allow immune cells to better recognize and attack cancer cells, may not provide the necessary boost to fighting cancer in elderly patients with aging immune cells. “The jury is still out on the role of immunotherapy, or specifically, checkpoint inhibitors in elderly patients,” says Dr. Barrick.

Dr. Barrick says research on the effect of immunotherapy on older patients is ongoing, but clinical data may be limited because older patients are less likely to volunteer for clinical trials. Additionally, elderly patients may have conditions such as chronic obstructive pulmonary disease (COPD) or heart failure that make them ineligible for clinical trials. “So we’re missing out on this very important group of patients,” Dr. Barrick says. However, doctors will continue to turn to immunotherapy when it is appropriate as a treatment option for patients of all ages, he says. “When you do well with one type of cancer, I don’t discriminate based on a person’s age,” says Dr. Barrick. “We still give them the doubt and test it when appropriate.”