Two drugs being developed by GlaxoSmithKline Plc - each designed to block different pathways used by cancer cells - have been shown in a small clinical trial to curb melanoma with fewer side effects than current therapies.
The experimental drugs are dabrafenib, designed to work in patients with a mutation of a gene known as BRAF, and trametinib, which interferes with a protein known as MEK. The drug combination was tested in patients with advanced melanoma and a mutation in the BRAF gene. About half of all melanomas - the deadliest form of skin cancer - have the genetic aberration.
Roche Holding AG's Zelboraf, or vemurafenib, is the only BRAF inhibitor approved for treating melanoma. It was shown in a pivotal trial to reduce the risk of death by 63 percent, but up to a third of patients who take the pill develop a less-deadly form of skin cancer known as cutaneous squamous cell carcinoma. In addition, most patients eventually develop resistance to the drug.
Researchers have theorized that other mutations, likely caused by sun exposure, could predispose BRAF-positive melanoma patients to squamous cell cancer, while treatment with a MEK inhibitor blocks that side effect.
The mid-stage trial of the Glaxo drugs included 77 patients not previously treated with a BRAF-targeted pill. The patients lived for a median of 7.4 months before their disease got worse. Two percent of trial patients developed squamous cell cancer and another 2 percent developed small pre-malignant lesions.
Other side effects included fever, fatigue and dehydration.
Within that group, 24 trial patients received a dose of the combined medication that researchers deemed optimal and which is now being used in more advanced trials. Those patients saw median progression-free survival of 10.8 months, Dr Jeffrey Weber of the H. Lee Moffitt Cancer Center in Tampa, Florida, who is also the study's lead author, said at a news conference held by the American Society of Clinical Oncology.
That compares with 7.4 months for a similar Phase II study of the Roche melanoma drug, he said. Glaxo has recently launched a pivotal study of its drug combination.
"We know that cancers are smart," said ASCO president-elect Dr Sandra Swain, who was not involved in the study. "They find work-around pathways. We are seeing a very innovative approach that ostensibly blocks off some of this pathway."
Melanoma is diagnosed in nearly 160,000 people worldwide each year. It can spread quickly to internal organs and average survival is six to nine months.