One-Two Melanoma Knockout Punch

Melanoma treatment with dabrafenib trametinib cocktail beats vemurafenib

(RxWiki News) Since basic research is made public, companies try to edge out the competition in other ways, trying combination therapies and slightly varying molecular structures for cancer drugs targeting the same mutations. 

The latest results from a clinical trial looking at cases of advanced melanoma showed that the new combination therapy developed by GlaxoSmithKline beat the competition by extending survival and lowering side effects.

"Ask your oncologist about combination therapy."

Researchers from the H. Lee Moffitt Cancer Center presented at the American Society of Clinical Oncology's annual conference and demonstrated that combining dabrafenib treatment with the skin cancer drug,

Trametinib extended the average survival of patients without cancer progression to 10.8 months.

These two drugs are under development by GlaxoSmithKline, and they target common mutations in melanoma. The BRAF inhibitor dabrafenib and MEK inhibitor trametinib beat the current approved melanoma drug Zelboraf (vemurafenib), with a much lower rate of side effects.

Similar to treatment with dabrafenib alone, studies on the BRAF inhibitor Zelboraf also showed an average gain of 7.4 months before cancer progression continued. Zelboraf was developed by the pharmaceutical corporation, Roche.

Initial studies on trametinib showed that while effective, resistance developed quickly.

Researchers got the idea to use both drugs together, hoping they would act as a one-two punch to eliminate skin cancer cells quickly before resistance developed.

A bonus discovered by the research was that side effects found in the study with combination therapy included only a four percent chance of developing other skin cancers, in addition to the usual side effects of fever, fatigue, and dehydration.

This was especially notable because studies on the competing drug Zelboraf showed that rather than four percent, up to a third of melanoma patients developed other skin cancers during drug administration.

Given that both dabrafenib and Zelboraf are similar drugs inhibiting the BRAF gene, the current theory is that adding trametinib blocked the development of other skin cancers, accounting for the drastically lower rate of squamous cell cancers in the new trial.

“It’s fascinating to find such promising effects with this combination regimen. Not only are the two drugs causing shrinkage of the cancer, but we’re seeing that a second anti-cancer therapy may actually suppress the side effects of the first,” said Jeffrey Weber, MD/PhD, lead author of the study and current director of the Donald A. Adam Comprehensive Melanoma Research Center.

The clinical trial was funded by GlaxoSmith Kline with some contribution provided by Bristol-Myers Squibb.

Research presented at conferences is considered preliminary until publication in a peer-reviewed journal.

Review Date: 
June 1, 2012