Two Drugs Shown to Prolong Survival in Advanced Melanoma Cases
SUNDAY June 5, 2011 -- Two new drugs prolong the lives of patients with advanced melanoma, one of the deadliest forms of skin cancer and one that is notoriously difficult to treat, let alone cure.
The first treatment, vemurafenib, inhibits a gene mutation harbored in half of all melanoma patients, but is not yet approved by the U.S. Food and Drug Administration. The other drug, Yervoy (ipilumumab), is an immune system therapy that won approval in March.
Research on both drugs was presented Sunday at the annual meeting of the American Society of Clinical Oncology in Chicago while also being published simultaneously online in the New England Journal of Medicine.
"This is really a huge step toward personalized care in melanoma," Dr. Paul Chapman, lead author of the first study and the attending physician in the melanoma/sarcoma service at Memorial Sloan-Kettering Cancer Center in New York City, said in a statement. "This [vemurafenib] is the first successful melanoma treatment tailored to patients who carry a specific gene mutation in their tumor, and could eventually become one of only two drugs available that improves overall survival in advanced cancers."
The second study was also led by doctors from Sloan-Kettering.
"Having two trials that show a benefit in survival in patients with melanoma, both of these in first-line settings -- we weren't here just a few years ago," said Dr. Stephen Hodi, director of the Melanoma Center at Dana Farber Cancer Institute in Boston. "These are huge, paradigm-shifting results for the field."
"The March FDA approval of ipilumumab [Yervoy] was the first new drug approval for melanoma in 13 years," said Tim Turnham, executive director of the Melanoma Research Foundation.
In the vemurafenib trial, sponsored by the drug's makers, researchers randomly assigned 675 patients with advanced, inoperable melanoma to receive either the chemotherapy drug dacarbazine or vemurafenib. Vemurafenib targets the V600E mutation in the BRAF gene.
At the three-month mark, patients taking vemurafenib were 63 percent less likely to die and 74 percent less likely to die or see their cancer return, compared to patients taking dacarbazine alone.
Few patients had side effects in the vemurafenib group, although some did develop squamous cell carcinoma, a less dangerous form of skin cancer.
This is the first drug that has been proven superior to chemotherapy in this group of hard-to-treat patients, the researchers said.
"There was such a substantial benefit that we recommended that patients cross over," Chapman said at a Sunday news briefing. "It's unprecedented to report a trial this early. The median follow-up time was three months." Yet the differences between the two groups became evident almost immediately.
Dr. Lynn Schuchter, co-moderator of the briefing and division chief of hematology-oncology at Abramson Cancer Center of the University of Pennsylvania in Philadelphia, said symptoms subsided in some patients almost immediately, enabling them to cut back on pain medication in just 72 hours.
"The median time to progression with dacarbazine was 1.6 months versus three months with vemurafenib, which is a huge difference," said Chapman.
In the second study, about 500 patients were randomly picked to receive Yervoy plus dacarbazine or dacarbazine alone.
Those taking both drugs lived a median of 11.2 months compared to 9.1 months for those taking dacarbazine alone. Time to recurrence of disease was about the same for both groups: 2.8 months and 2.6 months, respectively.
Almost half of those taking the combination therapy were alive after one year, compared to 36.3 percent in the other group. After two years, the rates were 28.5 percent and 17.9 percent, respectively.
By three years out, 20.8 percent of those in the combination group were alive compared with 12.2 percent of those taking chemotherapy alone.
The study was sponsored by Bristol-Myers Squibb, which makes Yervoy.
This is the first study to combine chemotherapy and immunotherapy both safely and effectively; a study to test vemurafenib in combination with Yervoy has already begun.
"Neither one are the real answers, but they are steps forward and that's what we need," said Turnham, who added that he thinks the real answers will come in combination therapies.
"We need to be nimble about combination studies," he said. "In the two years that we've known we need to study vemurafenib and ipilumumab [Yervoy], 18,000 people have died of melanoma in the U.S. We can't afford to wait. We're very excited about the positive news, but we have a long way to go."
The Skin Cancer Foundation has more on melanoma.
Posted: June 2011