Melanoma that metastasizes to the brain used to be among cancer’s most dismal and deadly diagnoses. New treatments, including precise radiation and drugs that stimulate the immune system, are improving patients’ chances and may directly benefit former President Jimmy Carter.
Carter’s melanoma was discovered during surgery on his liver, he said last week. The cancer has spread, and Carter said Thursday at a press conference that he will be treated with radiation for four small metastases in the brain. He also is taking a powerful new drug from Merck & Co., Keytruda, that may spur the immune system to kill cancer cells in the brain missed by radiation and that has been effective in many tumor types.
Carter is the highest-profile patient to receive Keytruda. Historically, patients with melanoma brain metastases were excluded from many cancer trials because researchers worried that drug molecules couldn’t easily cross the body’s protective barrier that shields the brain. Keytruda, though, stimulates immune-system cells, some of which may be able to reach the brain even if the drug itself can’t.
Carter is “receiving state-of-the-art care,” said Jedd Wolchok, a melanoma expert at Memorial Sloan Kettering Cancer Center in New York who isn’t involved in the former president’s treatment. “The most important advances in the treatment of melanoma in the last 10 to 15 years are being employed.”
Keytruda’s side effects include the potential for various immune-related problems, including thyroid disorders and liver, lung or colon inflammation.
Radiation technology has also come a long way from the old whole-brain standard. Now doctors are more likely to use targeted brain radiation, called stereotactic radiosurgery. Fast-dividing cells like cancer cells are more sensitive to the effects of radiation, which damages DNA.
Stereotactic radiosurgery focuses intense radiation specifically on tumors and works well in cases where there are a limited number of small tumors, researchers said. Wolchok said he had treated patients with melanoma brain metastases that have lived for years.
“Five years ago if you were diagnosed with brain metastases we would probably tell you that you had about six months to live,” said Anna Pavlick, who is co-director of the melanoma program at New York University’s Perlmutter Cancer Center. Now “the picture has totally changed.” Some patients in which the radiation therapy works “can go on to live normal, healthy lives for years.”
Combining radiation with an immune-boosting drug may enhance the effect of Keytruda, said Antoni Ribas, a melanoma expert at the University of California at Los Angeles who was involved in testing Merck’s drug. The radiation may induce changes in the tumor that make any leftover cancer cells more sensitive to the immune attack unleashed by the drug, he said.
The radiation “zaps what you see and the other turns on the immune system to kill what you cannot see,” he said.
There is limited data showing how well new immune-boosting melanoma drugs -- including Keytruda and Bristol-Myers Squibb Co.’s Opdivo -- will work for brain metastases. But some small studies suggest that the new immune-boosting drugs can help. Merck’s drug was approved for advanced melanoma in September.
In one study by Yale University doctors, partially funded by Merck, Keytruda significantly shrank tumors in four of 14 melanoma patients with brain metastases, according to data presented at the American Society of Clinical Oncology earlier this year.
Harriet Kluger, an oncologist at the Yale Cancer Center and lead author on the study, said the trial has since expanded its enrollment, and additional patients have had responses -- including some whose brain tumors vanished completely. An updated report will be presented in a few months, she said.
The fact that Carter’s tumors are small and were discovered early may help his prognosis, she said.
A 2012 trial of an older immune-boosting drug, Yervoy from Bristol-Myers, also found that the drug helped control melanoma brain metastases in 10 percent to 24 percent of the patients, with the results varying by the severity of the disease.