A new study offers a glint of hope to people in a desperate situation: Patients with melanoma, the most serious form of skin cancer, that has spread to the brain.
A combination of two drugs that activate the immune system shrank brain tumors in many melanoma patients and prolonged life in a study of 94 people at 28 medical centers in the United States. The drugs were ipilimumab (brand name Yervoy) and nivolumab (Opdivo), and they belong to a class called checkpoint inhibitors.
Melanoma is more likely than most cancers to spread to the brain, and once it gets there, fewer than 20 percent of patients survive one year with traditional treatments, according to Dr. Hussein A. Tawbi, the first author of the study and an associate professor of melanoma medical oncology at the MD Anderson Cancer Center in Houston.
But in the study, 82 percent were still alive after a year.
"This is great news," Dr. Tawbi said. "We can help a lot more melanoma patients, and hopefully we'll be able to help a lot more patients in general with these results."
About 91,270 new cases of melanoma are expected in the United States this year, along with 9,320 deaths from the disease.
Treating cancer that has spread to the brain is a new frontier for the type of drugs used in the study.
Checkpoint inhibitors enable the patient's own immune system to fight cancer, a treatment strategy called immunotherapy. They have led to long remissions from deadly forms of the disease, including melanoma and tumors in the lungs and kidneys. The drugs do not help everyone, but when they work the results can be remarkable.
The new findings should change the standard of care, Dr. Tawbi said: Melanoma patients like those in the study should be offered the drug combination as part of their initial treatment.
He said the drugs should also be tested in people with other types of cancer that have spread to the brain. He estimated that 200,000 people a year in the United States have brain tumors resulting from cancers in other parts of the body.
He emphasized that radiation would still be an important part of treatment for many of these patients.
The results do not apply to people with tumors that originate in the brain, like glioblastoma, the type of brain cancer that Sen. John McCain is being treated for. So far, the kind of immunotherapy used in the study has not worked for such tumors, Dr. Tawbi said, but studies of drug combinations are under way to try to help those patients.
The editorial, by doctors in Britain who agreed with Dr. Tawbi's recommendations, cautioned that the findings did not apply to all melanoma patients, only to those exactly like the ones in the study. Those patients had one or more brain tumors, detected by scans, that were not causing symptoms.
The drugs, made by Bristol-Myers Squibb, are expensive, costing more than $100,000 a year. The company paid for the trial, and helped to design it and to collect and analyze the data. The company also paid for medical writing and editorial assistance in preparing the article for the journal.
The National Cancer Institute also helped pay for the study.
Dr. Jedd Wolchok, a melanoma expert at Memorial Sloan Kettering Cancer Center in New York, said the findings had already been presented at a major cancer conference. "From the boots-on-the-ground point of view, this has changed the way I practice," he said.
The study, Dr. Wolchok said, made it clear that immunotherapy that was working to treat melanoma in other parts of the body could also control disease that scans had picked up in the brain.
He said brain tumors in one of his patients had disappeared with the treatment. And he agreed that immunotherapy should also be tested in patients with some other types of cancer that had spread to the brain.
"The survival outcomes are very encouraging," he said.
Dr. Wolchok's hospital participated in the study, but he was not involved in it.
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Until recently, patients with cancer that had spread to the brain were considered such hopeless cases that they were excluded from most clinical trials of new cancer drugs. They generally survived only weeks to months.
Radiation and surgery helped a bit, but the brain tumors generally came back. Patients deteriorated rapidly, and developed trouble thinking and moving around.
"The usual response from the oncologist and even the patient is nihilism," Dr. Tawbi said.
Immunotherapy caused excitement in 2015 when former President Jimmy Carter said he had received it after melanoma had spread to his liver and brain. He underwent radiation treatment as well.
His most recent scan, in June, showed no cancer, his press secretary, Deanna Congileo, said in an email. Mr. Carter received pembrolizumab (brand name Keytruda), a checkpoint inhibitor that was not used in the new study.
The drugs have side effects that can be serious and even life-threatening. A little more than half of the patients in the study had significant side effects, and 20 percent quit treatment because of them.
Some suffered from headaches, two had brain swelling, and one died from heart inflammation thought to be caused by the treatment.
Most melanoma cases can be cured with surgery if found early. But 10 percent to 15 percent of new cases are advanced when diagnosed, meaning that the disease has already spread to another organ, like the lungs or liver. Of the advanced cases, more than a third also have tumors that have spread to the brain, and up to 75 percent of these patients have brain malignancies when they die.
Until recently, patients with cancer that had spread to the brain were left out of treatment studies, partly because few cancer drugs can get into the brain, which is protected by blood vessels lined with tightly packed cells that keep out many molecules.
Even though immunotherapy and other new treatments that target certain mutations have greatly improved survival in melanoma patients, patients whose disease had reached the brain were still excluded from those studies.
But checkpoint inhibitors work by enabling T-cells — a type of white blood cell — to attack cancer. And T-cells do get into the brain.
Dr. Tawbi's study enrolled melanoma patients from February 2015 through June 2017. At first, only patients whose brain tumors did not cause neurologic symptoms were accepted.
Most had one or two brain tumors; 22 percent had three or more. Some had already been treated with other cancer drugs, and some had already had radiation for other brain tumors.
Partway through the study, patients with neurologic symptoms also were admitted to the study, but results on them are not yet available.
The study called for the patients to receive the drug combination at three-week intervals, four doses in all, and then to receive nivolumab alone every two weeks for a maximum of 24 months, or until the disease progressed, they had intolerable side effects, or they chose to quit.
About a third received all four combination doses, and 59 percent got nivolumab. The median number of nivolumab doses was 15. The overall median duration of treatment was 3.4 months.
With a median follow-up of 14 months, 57 percent of the patients were helped by the treatment: brain tumors disappeared in 26 percent and shrank in 30 percent. In another 2 percent, the tumors remained stable for at least six months.
In 56 percent, the treatment also worked against melanoma growths in other parts of the body. The estimated survival at one year was 81.5 percent.
Dr. Tawbi said the researchers now hope to determine the best way to use immunotherapy with radiation. "Instead of 57 or 58 percent, our goal is to reach 100 percent," he said.
— By Denise Grady, New York Times