Patients Over 80 Benefit from Immunotherapy for Certain Cancers, According to International Study Co-Led by OU Health Stephenson Cancer Center Physician

Patients 80 and older who are treated with single-agent immunotherapies for some cancers benefit from these innovative treatments and have somewhat comparable outcomes to younger people who received the same type of treatments for similar cancers, according to a landmark study published November 4, in the journal JAMA Oncology. Abdul Rafeh Naqash, M.D., a clinical trials physician at OU Health Stephenson Cancer Center, is senior author of the study, which suggests that older adults’ immune systems, when stimulated with immunotherapies, could indeed be up to the challenge of fighting certain types of cancers.

Immunotherapy drugs are anti-cancer agents that stimulate the body’s immune system to target and control tumors. These agents have shown promise in controlling some tumors more than others and have transformed the treatment landscape of some cancers over the past decade.

“Not all patients benefit from immunotherapy, which is why there is a significant need to understand which clinical and biological factors contribute to favorable or unfavorable outcomes for patients with cancer,” Naqash said.

An international team of physician-researchers, led by Naqash and his collaborator from Vanderbilt University, Caroline Nebhan, M.D., conducted the study. They were seeking to address a shortage of information that exists about treatment response, side effects and survival rates among people with certain types of cancer who are 80 or older and treated with immunotherapy. Although some cancer-related clinical trials enroll older patients, they tend to be age 65 to 75. Naqash estimates that less than 5% of cancer-related treatment trials involving immunotherapy include people over 80.

In this study, researchers retrospectively analyzed the outcomes of 928 patients with cancer, age 80 and older, who were treated with single-agent immunotherapies at 18 academic medical centers across the United States and Europe. Three types of cancer were primarily reviewed — non-small cell lung cancer, melanoma, and genitourinary tumors, including prostate, bladder and kidney cancer.

“We found that patients over age 80 had promising and comparable treatment response and survival, and no significant difference in side effects, compared to previously reported outcomes for younger populations with similar cancers,” Naqash said. “Because immunotherapy depends upon the patient’s immune system to activate anti-cancer effects, this study suggests that certain elements of the immune system maintain integrity even as we age.”

Often, oncologists prescribe combination therapies, such as chemotherapy with an immunotherapy drug, or two types of immunotherapy, to treat certain cancers. To keep comparisons uniform, Naqash’s research group only looked at patients receiving single-agent immunotherapies. Because of that sole focus, the study suggests a single-agent immunotherapy drug may be sufficient in some cases to prompt an immune response, control the cancer, and avoid the side effects associated with combination therapies, which is especially important in an age group that tends to be frail.

“Oncologists should have multidisciplinary, patient-centric discussions, taking into account the type of cancer, the patient’s functional status, their goals of care and any additional medical conditions, when deciding on a treatment course,” Naqash said. “Oncologists should not immediately lean toward palliative care or non-treatment simply because of a patient’s age,” Naqash said.

The study also showed that while patients 90 and older received benefits from immunotherapy, they also experienced slightly more side effects than those 80 to 90, and ultimately discontinued treatment earlier. This indicates that older adults may have a lower threshold for side effects and warrant closer monitoring while receiving immunotherapy, Naqash said.

Naqash’s study is considered a “proof of principle” publication, a necessary first step for advancing knowledge about cancer treatment in older patients. The next stage will be to create randomized clinical trials to further assess and validate the findings, by enrolling patients in the same age range and investigating specific types of cancer treated with immunotherapy. Naqash, in collaboration with colleagues at other institutions, also plans to analyze blood samples and genetic sequencing of tumors to better understand how the tumor microenvironment changes as people age. This information will be used to identify potential targets for treating various cancers.

Naqash’s current publication in JAMA Oncology, a top cancer research journal published by the American Medical Association, represents the most extensive study to date that elaborates on outcomes for adults 80 and older whose cancer was treated with immunotherapy. The study is also an important reminder that older patients are underrepresented in cancer clinical trials, he said.

“We should try to incorporate older patients in clinical trials whenever and wherever they can be,” he said. “By doing so, we will have better data so that physicians and their patients can make treatment decisions that are age-appropriate, rather than relying upon and extrapolating data that are primarily drawn from younger populations.”

Naqash is part of the Oklahoma TSET Phase 1 Clinical Trials Program at Stephenson Cancer Center, where he develops and conducts phase 1 clinical trials with the aim of creating innovative therapies to treat cancer and improve the lives of patients. He is known nationally for his work on cancer immunotherapy outcomes in unique patient populations, and he has led several international efforts to investigate immunotherapy-related side effects in patients with cancer.