* Trametinib PFS 4.8 months vs 1.5 months for chemo
* Dabrafenib PFS 5.1 months vs 2.7 months for chemo
By Deena Beasley
CHICAGO, June 4 Late-stage trials of two
experimental skin cancer drugs from GlaxoSmithKline,
each designed to block different pathways used by tumor cells,
have found the drugs helped patients with fewer side effects
than current chemotherapy.
Both drugs, trametinib and dabrafenib, were tested in
patients with a mutation in a gene known as BRAF. About half of
all melanomas, the deadliest form of skin cancer, have the
Cancer occurs through genetic changes in cells allowing
tumor growth factor receptors which activate various pathways,
including a protein known as MEK. It is believed that
BRAF-mutated melanomas should be particularly dependent on MEK,
which is needed to amplify the cancer's genetic signal.
Roche's Zelboraf, or vemurafenib, is the only BRAF
inhibitor currently approved for treating melanoma.
Latest results from a pivotal trial of the Roche drug,
presented at a meeting in Chicago of the American Society of
Clinical Oncology, found that it improved survival by nearly
But 19 percent of patients on Zelboraf developed a
less-deadly form of skin cancer known as cutaneous squamous cell
carcinoma and 10 percent developed another type of non-malignant
lesion. In addition, most patients eventually develop resistance
to the drug.
Removing the non-cancerous lesions is not a huge problem,
but a drug with fewer such side effects would be appealing, said
Dr. Kari Kendra, a melanoma specialist at Ohio State University
who was not involved in the studies.
"Anytime we don't have to be intrusive is a benefit," she
Citigroup has estimated Glaxo's annual sales for dabrafenib
and trametinib at 1.5 billion pounds ($2.35 billion) by 2020,
some three times the average of analysts' estimates.
Citi analyst Andrew Baum said dabrafenib was likely to be
launched in 2013 and would quickly erode sales of Roche's
In the trial of Glaxo's trametinib, which is designed to
interfere with MEK, patients given the drug lived for a median
of 4.8 months before their disease worsened, compared with 1.5
months for patients treated with standard chemotherapy.
The drug was associated with a 46 percent reduction in the
risk of death.
Side effects included skin rash in 7 percent of patients,
eye problems and high blood pressure.
The trial of dabrafenib, a BRAF inhibitor, found that
patients on the drug lived for a median of 5.1 months before
their disease worsened, compared with 2.7 months for the
Squamous cell carcinomas developed in 6 percent of the
dabrafenib patients, and 3 percent of them had photosensitivity.
Last month Glaxo announced results from a mid-stage trial
showing that patients treated with both trametinib and
dabrafenib lived for a median of 7.4 months before their disease
got worse. Two percent of patients developed squamous cell
cancer and another 2 percent developed small pre-malignant
Glaxo is conducting a pivotal trial of the combination
treatment and said it plans to file with the regulatory
authorities for approval of both drugs as single agent
About 160,000 new cases of melanoma are diagnosed each year
and 48,000 melanoma-related deaths occur worldwide each year.