New Therapies May Mean More Life for Patients with Advanced Melanoma
Two new drugs, vemurafenib (Zelboraf)
and ipilimumab (Yervoy), showing promise
in slowing the progression of this skin cancer
March 16, 2012 – A hot topic at the American Academy of Dermatology’s 70th Annual Meeting today was the
presentation on the recent reports of success in slowing deadly melanoma skin cancer – a major killer of senior men – with two new drugs,
vemurafenib (Zelboraf) and ipilimumab (Yervoy).
Melanoma, the most serious form of skin cancer, is highly curable when it is detected and treated early. The same is not
true for more advanced cases of melanoma - particularly when the disease has spread to lymph nodes or other areas of the body.
Recently, the two new drugs, both FDA approved to target the genetic makeup of melanoma, are showing promise in slowing
the progression of this disease and, in some cases, extending survival in patients with advanced melanoma.
Research has shown that certain melanomas have specific genetic abnormalities within the melanoma cells. With targeted
therapy, the abnormal gene responsible for these melanomas is targeted in an attempt to undo the damage it is causing the cells, according to
Darrell S. Rigel, MD, FAAD, clinical professor in the department of dermatology, NYU Langone Medical Center, New York, N.Y.
Dr. Rigel noted in his presentation that while a number of targets have been identified, a gene known as BRAF is mutated
in 40 to 80 percent of melanoma cells. This mutation causes the cells to grow uncontrollably and cancer to form.
► Vemurafenib: When a BRAF mutation is present, a pathway
known as the MAP Kinase Pathway essentially gets “stuck” in the “on” position and the cells start growing very rapidly. The drug vemurafenib
attacks the switch of this pathway (or blocks the “on” switch) so that the cells don’t continue to grow uncontrollably. If effective, the
cancer is prevented from getting worse.
● It's not a cure for melanoma, but researchers found during clinical trials that on average, patients who responded
lived 6.2 months without the melanoma getting worse.
● In some studies it was found that within six to 10 months on average, the melanoma cells develop resistance to the
drug. In this case, melanoma cells either develop other Kinase proteins to sidestep the pathway, or they simply use another pathway that is
not currently active. Either way, they activate to make cells continue to grow.
► Ipilimumab: This new targeted therapy blocks a specific
molecule, which may allow the patient’s body to recognize, target and attack melanoma cells. Researchers now are looking at using ipilimumab
in combination with vemurafenib, as they each block two different pathways – with the theory being that there is less chance for resistance to
● It's not a cure for melanoma, but researchers found during clinical trials that the patients who received only
ipilimumab and responded to it lived about 10 months longer. For a few patients given ipilimumab, the results were dramatic — a few patients
have had no signs of cancer for as long as six years.
Side Effects Can Pose Problems
Dr. Rigel cautioned that patients taking vemurafenib or ipilimumab may experience troublesome side effects and should be
closely monitored by their dermatologist.
● Studies have shown that significant rashes have been reported in approximately 40 percent of patients using
● One-third of patients taking vemurafenib developed multiple, aggressive squamous cell carcinomas (another common
type of skin cancer).
American Academy of Dermatology Expert Advice
“Before vemurafenib and ipilimumab were introduced, beating advanced melanoma used to be virtually hopeless and now there
is at least some hope for these patients,” said Dr. Rigel.
“Targeted therapy is still in its infancy, but already it has been successful in some cases of advanced melanoma. The
technique shows that it will work, and I expect we’ll see even more effective treatments in the future as we fine-tune our targeting of
The Academy urges everyone to examine their skin regularly. This means looking over your entire body including your back,
your scalp, your palms, your soles and between your toes. If you notice a mole different from others, or which changes, itches or bleeds, even
if it is smaller than 6mm, you should make an appointment to see a dermatologist.
Statistics: According to the American Cancer Society’s 2012 Cancer Facts and Figures:
● 9,180 Americans are estimated to die from melanoma in 2012.
● In 2012, it is estimated that the number of Americans diagnosed with melanoma will be 7 percent greater than in
● The five-year survival rate for localized melanoma is 98 percent, but the survival rate of distant, or advanced
stage, melanoma is 15 percent
Melanoma is the most serious type of
cancer and senior citizens are the usual victimes. 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.