GlaxoSmithKline’s (NYSE: GSK) combination of two experimental melanoma medicines slowed the progress of cancer with few skin complications in an early study, suggesting the combo may not have as many side effects as existing single- drug treatments.
Patients taking Glaxo’s dabrafenib and trametinib together had a lower incidence of rash and skin lesions than previously reported with Roche’s Zelboraf, according to a study of 77 patients with advanced melanoma, the most-severe form of skin cancer. The study, funded by Glaxo, was released Thursday ahead of the American Society of Clinical Oncology meeting that begins June 1 in Chicago. [GSK operates its U.S. headquarters in Research Triangle Park, N.C.]
“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, an oncologist at the H. Lee Moffitt Cancer Center in Tampa, Florida, in a statement. “So far it is looking good.”
If the Glaxo combination succeeds in final-stage trials, it would compete with Zelboraf, a targeted therapy cleared in August for sale in the U.S. Zelboraf and Glaxo’s dabrafenib work by blocking BRAF, a mutant gene that spurs cancer cell growth in about half of melanoma patients. Glaxo’s trametinib is designed to thwart a related protein called MEK, which helps tumors resist an assault on BRAF.
Adding the MEK drug may reduce a signature side effect of BRAF drugs like Zelboraf, the development of non-melanoma skin cancer, while possibly boosting efficacy, said Weber, a study leader, in a telephone interview. Weber has consulted for Glaxo and Basel, Switzerland-based Roche.
About 15 to 30 percent of melanoma patients treated with Zelboraf and other BRAF inhibitors develop non-melanoma skin cancers, scientists at the Institute of Cancer Research said in an article published in the New England Journal of Medicine in January. The drugs speed a type of skin malignancy known as squamous-cell carcinoma in patients who may have gotten the cancer anyway, they said.
Only 3 percent of a larger group of patients in the Glaxo combo study, which also included other solid tumors, developed squamous cell carcinoma, and 5 percent developed premalignant lesions called actinic keratoses, Weber said.
Across various doses, the combination delayed progression of the disease by 7.4 months. In the high-dose level, which will be studied in further trials, the two-drug therapy delayed the progression of the disease by 10.8 months, Weber said.
Roche’s Zelboraf delayed melanoma tumors from progressing for 6.8 months in one early trial and 5.3 months in a final- stage trial.
“It would look clearly superior to the figure we have seen” with the Roche drug, Weber said on a conference call with reporters. “It is a very impressive record by any criteria.”
Charlotte Arnold, a spokeswoman for Roche, said in an e- mail that “it is not appropriate” to compare data from Zelboraf’s approval trials with results from the early study of Glaxo’s combination, as it didn’t directly compare the drugs. Zelboraf has been proven to extend survival of melanoma patients.
Glaxo plans to start a final-stage trial “as early as this month” said Melinda Stubbee, a spokeswoman for the British drugmaker, in a phone interview. The trial would compare the combination to Glaxo’s dabrafenib alone in melanoma patients.
Glaxo also has also been studying each drug separately for melanoma and will seek regulatory approval of both compounds individually later this year.
Melanoma strikes 68,000 Americans each year, according to the American Cancer Society. While patients with early stage disease respond well to treatment, the five-year survival rate for those with cancer that has spread is 15 percent.
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