Melanoma kills about 9,000 Americans each year, and it often progresses quickly. Studies have found that the midpoint in survival time for patients on standard chemotherapy is just six to 10 months for patients with melanoma that has spread to other organs.
Last year, the FDA fast-tracked approval for Zelboraf, a pill that targets a specific mutation in the BRAF gene that’s present in about half of all melanomas.
At the time it was approved, studies showed the drug was shrinking tumors in most patients who took it, but researchers had not been following patients long enough to know how it might affect long-term survival.
The new study, which is published in the New England Journal of Medicine, followed a group of 132 patients taking Zelboraf for an average of 13 months.
Drug May Buy Patients More Time
More than half of the patients in the study saw their tumors shrink by at least 30%. In another 33% of patients, the drug slowed or stopped the progression of their disease. Only 14% of patients didn’t appear to see any benefit from the drug.
As dramatic as the responses to Zelboraf can be, they may not last. By seven months, half the patients in the study had stopped responding to the medication.
But even a temporary response appears to extend survival. Half the patients in the study were still alive after 16 months.
“There’s a feeling that patients respond for a very short time and then relapse. Obviously that’s true, there are patients like that. But there is a group of patients who respond for much longer periods of time, and a number of patients are still alive at a year or two years. And I think we didn’t appreciate those numbers before,” says researcher Jeffrey A. Sosman, MD, director of the melanoma and tumor immunotherapy program at the Vanderbilt-Ingram Cancer Center in Nashville, Tenn.
The study was paid for by Hoffmann-La Roche, the company that makes the drug.
In addition to giving patients more time, researchers say the drug, which costs about $9,400 a month, helps people feel better for longer.
“We get some great responses initially, at least, so we can talk to patients with a smile compared to two years ago; it was a pretty much pessimistic view of the outcomes,” says researcher Kevin B. Kim, MD, an associate professor of melanoma medical oncology at The University of Texas MD Anderson Cancer Center in Houston.
For patients with large tumors who are suffering from pain and discomfort, “We can shrink tumors significantly, so the pain can be improved quite dramatically,” Kim says. “People feel stronger very quickly.”
Side Effects ‘Not Trivial’
Along with those benefits, the drug does come with some significant side effects.
“The side effects are certainly reasonable for a cancer drug. They’re not trivial,” Sosman says. “A number of patients needed to have their drug held for a short time or needed to have their dose lowered, but almost all patients continued on the drug. Few stopped it.”
The most problems seen in patients taking the drug were joint pain, rash, skin that easily burns in the sun, fatigue, and hair loss. More than a quarter of patients who take the drug also develop new squamous-cell skin cancers, although those are thought to be less dangerous than the melanoma.
“These patients should be followed closely by a dermatologist, which is probably a good idea anyway,” Sosman says.
Experts who were not involved in the study said the results mark an important advance in treating melanoma, but noted that there was much more work to be done to understand why people develop resistance to the drug and eventually relapse.
“This is a very exciting drug in the sense that it provides almost all patients with BRAF-mutated melanomas a remission,” says Kim A. Margolin, MD, who leads melanoma research for the Seattle Cancer Care Alliance.
“There’s no remote chance this is going to be a cure. There may be 1% or 2% of patients who remain in very durable remissions, but everyone is scratching their heads about why they haven’t developed resistance the way everyone else has,” says Margolin, who is also a professor at the University of Washington and a member of the Fred Hutchinson Cancer Research Center, both in Seattle.
Patient advocates still see a reason for hope.
“We can see a time when for most patients, melanoma will become a curable or a manageable disease,” says Tim Turnham, executive director of the Melanoma Research Foundation. “We’re not there yet, and we’re not close to there yet, but we can see that we can get there.”