Why Cancer Treatments Might Not Work Very Well for Older Adults

Fernando Kaskais

Jun 29

Top: A senior cancer patient receives chemotherapy. Many forms of chemotherapy have proven to be more toxic in older adults, a discovery that came only after the drugs were approved for use in this population. Visual: E+ via Getty Images

People over 70 have a heightened risk of cancer, yet they are under-represented in clinical trials of new drugs.

BY JYOTI MADHUSOODANAN

IN OCTOBER 2021, 84-year-old Jim Yeldell was diagnosed with stage 3 lung cancer. The first drug he tried disrupted his balance and coordination, so his doctor halved the dose to minimize these side effects, Yeldell recalled. In addition, his physician recommended a course of treatment that included chemotherapy, radiation, and a drug targeting a specific genetic mutation. This combination can be extremely effective — at least in younger people — but it can also be "incredibly toxic" in older, frail people, said Elizabeth Kvale, a palliative care specialist at Baylor College of Medicine, and also Yeldell's daughter-in-law.

Older patients are often under-represented in clinical trials of new cancer treatments, including the one offered to Yeldell. As a result, he only learned of the potential for toxicity because his daughter-in-law had witnessed the treatment's severe side effects in the older adults at her clinic.

This dearth of age-specific data has profound implications for clinical care, as older adults are more likely than younger people to be diagnosed with cancer. In the U.S, approximately 42 percent of people with cancer are over the age of 70 — a number that's poised to grow in the years to come — and yet they comprise less than a quarter of the people in clinical trials to test new cancer treatments. Those who do participate are often the healthiest of the aged, who may not have common age-related conditions such as diabetes or poor kidney or heart function, said Mina Sedrak, a medical oncologist and the director of the Cancer and Aging program and the University of California Los Angeles.

For decades, clinical trials have tended to exclude older participants for reasons that range from concerns about pre-existing conditions and other medications to participants' ability to travel to trial locations. As a result, clinicians have little way of being certain that approved cancer drugs will work as predicted in clinical trials for the people most likely to have cancer. This dearth of data means that older cancer patients must decide if they want to pursue a treatment that might yield fewer benefits — and cause more side effects — than it did for younger people in the clinical trial.

This evidence gap extends across the spectrum of cancer treatments — from chemotherapy and radiation to immune checkpoint inhibitors — with sometimes dire results. Many forms of chemotherapy, for example, have proven to be more toxic in older adults, a discovery that came only after the drugs were approved for use in this population. "This is a huge problem," Sedrak said. In an effort to minimize side effects, doctors will often tweak the dose or duration of medications that are given to older adults, but these physicians are doing this without any real guidance.

Despite recommendations from funders and regulators and extensive media coverage, not much has changed in the past three decades. "We're in this space where everyone agrees this is a problem, but there's very little guidance on how to do better for older adults," Kvale said. "The consequences in the real world are stark."

POST-APPROVAL STUDIES of cancer drugs have helped shed light on the disconnect between how these drugs are used in clinical trials and how they are used in clinics around the country.

For example, when physician and cancer researcher Cary Gross of Yale University set out to study the use of a new kind of cancer drug known as an immune checkpoint inhibitor, he knew that most clinicians were well aware that clinical trials overlooked older patients. Gross' research team suspected that some doctors might be wary of offering older adults the treatments, which work by preventing immune cells from switching off, thus allowing them to kill cancer cells. "Maybe they're going to be more careful," he said, and offer the intervention to younger patients first.

Older cancer patients must decide if they want to pursue a treatment that might yield fewer benefits — and cause more side effects — than it did for younger people in the clinical trial.

But in a 2018 analysis of more than 3,000 patients, Gross and his colleagues found that within four months of approval by the U.S. Food and Drug Administration, most patients eligible to receive a class of immune checkpoint inhibitors were being prescribed the drugs. And the patients receiving this treatment in clinics were significantly older than those in the clinical trials. "Oncologists were very ready to give these drugs to the older patients, even though they're not as well represented," Gross said.

In another analysis, published this year, Gross and his colleagues examined how these drugs helped people diagnosed with lung cancer. The team found that the drugs extended the life of patients under the age of 55 by a median of five months, but only by a month in those over the age of 75...

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