Drug Combo Fights Melanoma That Has Spread to Brain

hospital patient in bed
hospital patient in bed

THURSDAY, Aug. 23, 2018 (HealthDay News) -- A combination of two drugs that work with the immune system can help beat back melanoma that has moved to the brain, an early clinical trial has found.

The study included 94 patients with advanced melanoma that had invaded the brain. All were treated with two "immunotherapy" drugs -- Opdivo (nivolumab) and Yervoy (ipilimumab) -- which help the immune system find and destroy tumors.

Overall, 57 percent of the patients saw their brain tumors disappear, shrink or remain stable for at least six months. For most, the responses were still evident at their latest follow-up, at the 14-month mark.

And after one year, more than 80 percent of all patients were still alive.

"That's really tremendous," said lead researcher Dr. Hussein Tawbi, of the University of Texas M.D. Anderson Cancer Center in Houston. "Without treatment, that rate would be about 20 percent."

Experts said the findings represent another step forward against advanced melanoma, the deadliest form of skin cancer. Once melanoma spreads to distant sites in the body, the prognosis has traditionally been grim. When it infiltrates the brain, the typical life expectancy has hovered around four to five months, according to Tawbi.

But in recent years, several new drugs have been approved to fight advanced melanoma. They include Opdivo and Yervoy, which are already used in combination.

The drugs belong to a group of immunotherapies called checkpoint inhibitors. They essentially free up immune-system T-cells to seek and destroy tumor cells.

But major trials of the drugs, Tawbi said, have excluded patients with brain metastases (melanoma that has spread to the brain).

Right now, he said, the typical treatment for those patients is surgery to remove the tumors, if possible, as well as radiation. Then they might receive immunotherapy drugs.

Tawbi's team took a different approach: They used Opdivo and Yervoy as a first-time treatment for patients with brain metastases that were discovered during MRI scans.

All received infusions of both drugs every three weeks, for up to four doses. After that, they continued with Opdivo infusions every two weeks, until their cancer progressed or the side effects became too toxic. Opdivo maker Bristol Myers-Squibb partially funded the trial.

"Our first concern was whether it would be safe," Tawbi said.

One worry was that if T-cells flooded the brain to attack the cancer, it would cause dangerous brain inflammation.

But, Tawbi said, the side effects were similar to what's seen in melanoma patients without brain metastases. Most often, that meant fatigue, diarrhea, nausea and increases in liver enzymes that can indicate liver damage.

One patient died of a heart complication blamed on the treatment. And 20 percent went off the drugs because of severe side effects.

As for the benefits, 26 percent of patients saw their brain tumors disappear. Tumors shrank in another 30 percent, and two patients remained stable for at least six months.

The overall survival rate at one year was 81.5 percent.

"That's exactly what you'd expect to see in patients without brain metastases," said Dr. Mario Sznol.

Sznol is a melanoma expert with the American Society of Clinical Oncology, and co-directs the cancer immunology program at Yale Cancer Center in New Haven, Conn.

He said the findings suggest that many patients with brain metastases can skip radiation -- and its side effects -- and go straight to immunotherapy.

That's not true of all patients, stressed Sznol, who was not involved with the study. The trial did not include people with large brain tumors, for example -- which may require surgery and radiation first.

The immunotherapy drugs do have a high rate of side effects, Sznol noted, but those problems are usually medically manageable.

The drugs are also very pricey: The list price for the first year of therapy with both tops $250,000.

But on balance, Sznol said, "I think the risk-benefit ratio falls in favor of treatment."

A couple of small trials have tested the effects of Opdivo or Yervoy alone in patients with brain metastases, but only about one-quarter responded, according to Tawbi.

So, he said, the combination appears more effective.

Sznol said the findings offer a hopeful message to patients.

"It's becoming a myth that melanoma patients with brain metastases will do poorly," he said. "Some will. But that's not necessarily the case anymore."

The study was published Aug. 23 in the New England Journal of Medicine.

More information

The American Society of Clinical Oncology has more on immunotherapy for melanoma.

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