Metastatic Melanoma Patients Live Almost Twice as Long with New Drug
Zelboraf (vemurafenib) changes the natural history of the disease to extend survival - see video
A researcher describes the results
Feb. 23, 2012 - A new drug for patients with metastatic melanoma – mostly older men - nearly doubled median overall
survival. More than half of patients who were treated with the drug vemurafenib, known commercially as Zelboraf, responded to treatment and
experienced an impressive median overall survival of nearly 16 months – far longer than the typical survival of just six to 10 months for most
patients whose melanoma has spread beyond the initial tumor site.
Results from the Phase 2 trial, led by co-principal investigators Jeffrey Sosman, M.D., director of the Melanoma Program
and co-leader of the
Transduction Program at Vanderbilt-Ingram Cancer Center,
and Antoni Ribas, M.D., professor of Hematology/Oncology at UCLA’s Jonsson Comprehensive Cancer Center, were published in the Feb. 23 issue of
the peer-reviewed New England Journal of Medicine.
National Cancer Institute
Definition of melanoma: A form of cancer
that begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also
begin in other pigmented tissues, such as in the eye or in the intestines.
Estimated new cases and deaths from
melanoma in the United States in 2012:
> New Cases: 76,250
> Deaths: 9,180
“This study confirms what we have discovered in our earlier trials. Many of our patients are exhibiting a strong,
immediate response to this drug and some are living significantly longer, with manageable side effects,” said Sosman, professor of Medicine at
Vanderbilt University Medical Center.
“It was interesting to note that a few of the patients were treated with the drug for up to six months before showing
convincing evidence of response.”
“This study shows that Zelboraf changes the natural history of the disease,” said Ribas. “These results tell us that this
drug is having a very big impact, and this changes the way we treat metastatic melanoma.”
Approximately half of all patients with metastatic melanoma – the most deadly form of skin cancer – have a BRAF V600
mutation in their tumor. Vemurafenib is an FDA-approved oral drug which works as a kinase inhibitor of the BRAF V600 mutation.
While vemurafenib induced clinical responses in a significant number of BRAF-positive patients when it was approved last
year, the initial clinical trials had not followed patients long enough to determine overall survival.
A total of 132 patients with stage IV, BRAF-positive melanoma were enrolled in the Phase II trial. All of the patients
had received at least one form of systemic treatment before enrollment in the trial.
Forty-seven percent of patients had a partial response to the drug and six percent exhibited a complete response, for an
overall response rate of 53 percent.
Debra Johnson’s melanoma had already spread to one of her lungs and her lymphatic system when she was referred to VICC
for mutation testing. Her tumor was BRAF-positive and after more than a year on the drug, the wife and mother from New Site, Miss., says her
scans are clear and there is no visible evidence of disease.
“This treatment has been an answer to my prayer,” said Johnson.
The majority of patients had at least one adverse event related to the drug, but most of these were minor. The most common side effects were
joint pain, rash, sun sensitivity, fatigue and hair loss.
More than a quarter of the patients (26 percent) also developed cutaneous squamous-cell carcinomas – a less serious form
of skin cancer - which were surgically removed.
A Phase III trial of this same drug confirmed significant improvement in both progression-free survival and overall
survival with vemurafenib over chemotherapy in an interim analysis. The Phase II study is the first to confirm the durability of the response.
While the clinical trials for vemurafenib have been positive to date, the great majority of patients eventually
experience disease progression.
“We are trying to determine what is causing this drug resistance and are searching for new therapies that we can use,
perhaps in combination with vemurafenib,” said Sosman.
Zelboraf was approved by the U.S. Food and Drug Administration for use in metastatic melanoma in August 2011. About
70,000 new cases of melanoma are diagnosed each year in the U.S. Of those individuals, 8,000 will die of the disease.
The Phase III research was funded by
Pharma. Thirteen centers in the United States and Australia participated in the research.
after removal of melanoma from top of senior citizens head
Melanoma is the most serious type of
cancer. Often the first sign of melanoma is a change in the size, shape, color or feel of a mole. Most melanomas have a black or
black-blue area. Melanoma may also appear as a new mole. It may be black, abnormal or "ugly looking."
Thinking of "ABCD" can help you remember what to watch for:
● Asymmetry -
the shape of one half does not match the other
● Border - the
edges are ragged, blurred or irregular
● Color - the
color in uneven and may include shades of black, brown and tan
● Diameter -
there is a change in size, usually an increase
Melanoma can be cured if it is diagnosed and treated early. If melanoma is not removed in its early
stages, cancer cells may grow downward from the skin surface and invade healthy tissue. If it spreads to other parts of the body it can be
difficult to control.
Couples encouraged to examine each other for
suspicious moles that could be skin cancer. Researchers estimate that 40
– 50% of people in the U.S. who live to age 65 will have nonmelanoma
skin cancer at least once.