An experimental targeted cancer drug shrank advanced melanoma tumors in 81 percent of patients with the deadly and hard-to-treat cancer, doctors said Wednesday.
The findings were part of an early phase study used to determine the best dose of the experimental drug PLX4032, now in late-stage clinical trials. It is designed to target tumor cells with a mutation in a gene called BRAF. The drug is made by Roche and privately held Plexxikon.
In two patients, tumors went away completely. In 24 others, the tumors shrank by more than 30 percent, the team reported in the New England Journal of Medicine.
The team said 81 percent of 32 patients with a BRAF mutation showed complete or partial shrinkage of their tumors.
"We can see the improvement in patients and it's happening quite rapidly, within a week or two of starting treatment," Dr. Keith Flaherty of the Massachusetts General Hospital in Boston said in a telephone interview.
"For patients without symptoms, the hope is that it delays the time it takes for them to develop symptoms, and we have some belief that that is happening as we speak," said Flaherty, who worked on the study.
But the effect appears to be fleeting.
In all but two cases, where the cancer has stayed away for at least a year, the benefits have been temporary, typically lasting about six months, Flaherty said.
The hope is that the drug can be combined with other treatments to produce a long-lasting effect, comparable to the AIDS cocktail that maintains the health of many people with HIV, he said.
Preliminary findings with the new drug were reported in September 2009, but the data from more patients have been added, boosting confidence in its prospects.
Tumors shrank at all sites where the tumor had spread, including the bone, liver and small bowel.
Cancer-causing mutations in the BRAF gene occur in 50 percent to 60 percent of melanoma patients.
Second drug
Researchers are eager to test the drug with Bristol-Myers Squibb's experimental drug ipilimumab, the first treatment shown to extend lives of patients with advanced melanoma.
In June, researchers reported that more than 20 percent of patients with advanced melanoma were alive two years after treatment with ipilimumab — compared with a usual nine months.
Ipilimumab or "ipi" is a monoclonal antibody, an engineered version of a human protein that targets CTLA-4, a molecule that acts like a brake on the immune system.
"The data provided by Flaherty and colleagues represent a major advance in the treatment of metastatic melanoma," Keiran Smalley and Dr. Vernon Sondak of Moffitt Cancer Center and Research Institute in Tampa, Florida, said in a commentary in the same journal.
Side effects included rash, fatigue, joint pain and a high risk of a different type of skin cancer known as cutaneous squamous-cell carcinoma. Of 87 patients enrolled in both stages, 18 developed such tumors, which are easier to treat.
The BRAF mutation is also found in about 8 percent of solid tumors, suggesting the drug might be effective in other forms of cancer.
Melanoma is the most aggressive form of skin cancer, affecting 160,000 people worldwide each year. When melanoma has spread, conventional chemotherapy is typically effective only in 10 percent to 20 percent of the cases.