Study: Immunotherapy shrinks melanoma
Drugs show promise against cancer that had spread to patients’ brains
A combination of two drugs that enlist the immune system to fight cancer shrank melanoma that had spread to the brain in most patients, according to a Houston-led study that provides another sign of immunotherapy’s promise.
The study provides hope the cutting-edge therapy pioneered by MD Anderson Cancer Center scientist Jim Allison could help treat many brain cancer metastases, typically a last stage of the disease. The cancers of about 200,000 U.S. patients spread to the brain annually.
“This opens the door to investigate other cancers where there’s brain metastasis, to start proving whether combination immunotherapy works in them, as well,” said Dr. Hussein Tawbi, an MD Anderson melanoma oncologist and principal investigator of the study, which was conducted at 28 U.S. sites.
Tawbi called the study, published Wednesday in the New England Journal of Medicine, “practice-changing” and said it will have an immediate impact on melanoma, the deadliest form of skin cancer. Once melanoma spreads to the brain, fewer than 20 percent of patients survive a year with traditional treatment. Eighty-two percent of the 94 patients in the study were still alive after a year.
Immunotherapy’s success against melanoma has been well documented, but patients whose disease
spreads to the brain remain the most in need, routinely excluded from clinical trials due to the severity and presumed intractable nature of their disease. Tawbi said they have “the worst prognosis.”
Former President Jimmy Carter is the best known beneficiary of immunotherapy for melanoma that has spread to the brain. Carter, 93, initially had said he felt he “had just a few weeks left” after that diagnosis in August 2015, but he now is cancer free following treatment with an immunotherapy drug.
Melanoma is expected this year to be diagnosed in more than 91,000 Americans and kill 9,300, according to the American Cancer Society. The disease already has spread to the brain at diagnosis in about 40 percent of Stage 4 melanoma patients and it eventually reaches there in about 75 percent of such patients.
The study enlisted two checkpoint inhibitor drugs — ipilimumab and nivolumab — which release a natural brake that otherwise reins in the immune system. Allison discovered the brake and developed ipilimumab, the first such drug, jump-starting the field of immunotherapy, until then thought to be a lost cause. The approach now is considered a fourth modality of cancer treatment, along with surgery, radiation and chemotherapy.
Checkpoint inhibitor drugs still only work in a minority of cancers and patients, but they frequently produce lasting results not seen from other treatments.
The study found brain metastasis had not progressed nine months after treatment in 60 percent of trial participants. Currently, average survival for patients with brain metastases is four to five months. It showed a similar benefit in the patients’ melanoma in the rest of the body.
The fortunate participants included Houston’s Colleen Wittoesch, who was found to have 12 tumors in her brain in 2016 after her grown children called attention to how forgetful and incoherent she had become. She jumped at the chance to try immunotherapy and 12 months later her doctors reported her cancer was completely gone. It remains gone more than a year later.
“It was God-sent, a miracle,” said Wittoesch, 55. “I knew the original diagnosis was not good, that I was in for a big fight. But once I got on immunotherapy, I felt like I had a chance. It’s given me a second chance at life.”
Wittoesch, a former volunteer in MD Anderson’s melanoma clinic, suffered headaches from the immunotherapy the first seven months. She said she could feel her immune system attacking the tumors. Side effects were a major concern going into the study because checkpoint inhibitors often cause inflammation and swelling, potentially dangerous inside the skull. Tawbi, however, said the therapy proved remarkably safe in the trial, inducing brain swelling less than 5 percent of time.
An accompanying editorial in the journal cautioned that the study findings apply to a subset of melanoma patients — those with one or more brain tumors, not previously treated and not causing symptoms — not all such patients. They do not apply to people whose tumors originate in the brain, such as glioblastoma, the type that killed Sen. Edward Kennedy and for which Sen. John McCain is undergoing treatment.
Tom Halkin, communications manager for the National Brain Tumor Society, said the study and other mounting evidence shows that patients with brain metastases no longer should be automatically excluded from clinical trials of checkpoint inhibitors. He noted the study was conducted by “a top-class group of researchers from a number of really reputable institutions.”
Tawbi said the trial proves doctors can use immunotherapy as a first-line treatment of melanoma that has spread to the brain rather than require the patient first undergo radiation and surgery. He said it should cause reconsideration of that standard, though he emphasized that radiation should remain an important treatment for many patients.
“We are very excited about these results,” he said. “They show you don’t have to wait for radiation, you can initiate immunotherapy early for all patients and expect the tumors in the brain to respond as well as those outside the brain.”