How Jimmy Carter boosted a life-saving cancer drug


When Norman C. Sharpless, former director of the National Cancer Institute, told members of Congress about the exciting new developments in immunotherapy, “their eyes immediately rolled to the back of their heads,” he recalled.

But when Sharpless described the treatments as “this drug that Jimmy Carter took, ‘Boom, they knew exactly what I was talking about,'” he said.

In December 2015, news that Carter, then 91, had recovered from advanced melanoma – previously on death row – gripped the country. Instantly, he became the face of a revolutionary approach to the fight against cancer, which kills more than 600,000 people a year in the United States. Here is a beloved figure, seemingly cured of a fatal disease by a drug that had harnessed Carter’s own immune system.

“For the public, Carter put immunotherapy on the map, period,” said Drew M. Pardoll, director of the Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins. “Patients started asking for it.” It was called the “Jimmy Carter effect”.

Even some oncologists were surprised by Carter’s stunning recovery. “It was like, ‘Holy smoke, this stuff really works,'” Sharpless said.

Carter was diagnosed in August 2015 with metastatic melanoma – skin cancer that had spread to her liver and brain; he later said he assumed he had only weeks to live. But in addition to radiation therapy, he was given a new intravenous drug called a “checkpoint inhibitor.” These drugs target proteins – checkpoints – that keep the immune system in check, but can also dampen the body’s response to fight cancer.

The result shed light on cancer drugs that don’t directly target cancer, but rather unleash the immune system to attack malignant tumors. At Carter, all signs of cancer were gone by the end of 2015 and her treatments were stopped soon after.

Carter, now 98, recently entered palliative care, which is designed to make patients comfortable at the end of life while avoiding efforts to cure the disease. He did not provide details of his condition or whether his cancer had returned. But several immunotherapy experts said it was unlikely the disease would return, given he had been cancer-free for several years.

“The odds are low that it’s a recurrence,” Pardoll said. In recent years, the former president has experienced other health setbacks, including several falls.

Carter’s 2015 recovery from deadly cancer electrified the public and the oncology community, helping to redefine the priorities of government funding and pharmaceutical research. Today, checkpoint inhibitors are approved for more than 20 malignancies, including kidney, head and neck cancers, and some lung cancers, often in combination with chemotherapy and other drugs. The percentage of patients eligible for the therapy, first approved in 2011, had risen to around 38% by 2019, according to an estimate published in the journal JAMA Network Open. About 1.9 million cases of cancer will be diagnosed this year.

Public and private insurers typically cover drugs, whose list prices are often well over $100,000 a year. Patients’ out-of-pocket expenses vary depending on their health plans.

Although oncologists claim that immunotherapy has transformed cancer care, curing some patients and extending the lives of many others, they agree that it is far from a silver bullet. According to studies, patient response rates vary widely – from around 10% to 60% – depending on their type of cancer and whether the drug is combined with other treatments.

“A lot of us were hoping it would work out better,” Sharpless said. “No one is throwing in the towel, but it turned out to be harder than we thought.”

Hussein A. Tawbi, a melanoma expert at the MD Anderson Cancer Center in Houston, agreed that scientists are making great strides with immune therapies, but warned that “we are still leaving a lot of patients behind.”

Because of this, researchers are intensifying their focus on why immunotherapy works in some patients — and against some tumors — but not others. Tawbi focuses on how immunotherapy can be used to treat cancers that have spread to the brain. About 30% of cancer patients develop brain growths, which can lead to slurred speech and headaches.

The idea of ​​using the immune system to fight cancer has been around for decades. More than a century ago, New York surgeon William Coley, now known as the father of cancer immunotherapy, treated patients with dead bacteria to trick the immune system into attacking cancer cells.

Over the next few years, scientists explored immunotherapy, but the resulting drugs were largely ineffective and highly toxic. the field was widely considered a backwater. That changed in 2011, when the Food and Drug Administration approved the first checkpoint inhibitor, called ipilimumab, or Yervoy. The drug blocks CTLA-4, a protein in immune cells that cripples their ability to attack cancer.

The drug was based on the findings of scientist MD Anderson James P. Allison, who was awarded the Nobel Prize in 2018 along with Japanese cancer researcher Tasuku Honjo. The two won the award for studies leading to breakthrough drugs that help the immune system fight cancer.

The drug given to Carter in 2015, called pembrolizumab, or Keytruda, was approved in 2014. The Merck drug, which has become a major oncology hit, blocks a checkpoint called PD-1 and is used to treat many types of cancers.

In recent years, immune therapies have proliferated, becoming the fourth pillar of cancer treatment, alongside surgery, radiotherapy and chemotherapy. In addition to checkpoint inhibitors, a treatment called CAR T-cell therapy that was approved in 2017 is sometimes used for blood cancers such as leukemia and lymphoma. A patient’s immune cells are removed, re-engineered in the lab to destroy the cancer, and injected back into the body.

Checkpoint drugs had their greatest effect in advanced melanoma. “It changed the paradigm,” said Cary P. Gross, professor of medicine at Yale School of Medicine. Before drugs were developed, patients usually survived a few months. Now the five-year survival rate is about 50%.

But drugs are not a miracle cure. About half of patients with advanced melanoma do not respond. And treatments have generally not proven effective in fatal malignancies such as pancreatic cancer and glioblastoma, which affects the brain. Their record is mixed against lung cancer, the leading cause of death among cancers in the United States.

Gross thinks “we may have to lower our expectations” about immune therapies, but they will improve in the coming years.

Regardless of drug developments, Carter, a longtime Sunday school teacher, taught the public important lessons about new treatments and the hope they can bring, Gross said. More recently, he added, Carter underscored the value of palliative care by going public with his decision on end-of-life care.

By sparking conversations about these critical issues, Gross said, Carter “taught us so much,” including how he wants to spend his final days.

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