Melanoma cocktail slows cancer’s growth

The combination of 2 GlaxoSmithKline drugs slows down skin cancer’s growth, early results from a new clinical trial show.

Drug resistance is a major problem with melanoma treatments… the cancer has the ability to evade therapy aimed at a tumor’s molecular weak spot. But by combining high doses of 2 new drugs against advanced melanoma, scientists were able to delay the cancer’s evasive tactics – slowing the tumor’s progress by several months. ScienceNOW reports.

The trial tests a BRAF inhibitor – a new type of skin cancer drug that targets a growth-spurring protein, called BRAF, which is encoded by a mutation on a gene that occurs in half of melanoma patients.

Roche’s Zelboraf (vemurafenib) was cleared for sale last August. Patients on the drug live 14 to 15 months on average, compared with the 8 months on conventional chemotherapy. However, the tumors eventually develop resistance and begin growing again.

Often the tumors restore the BRAF growth pathway by turning on a downstream protein called MEK, suggesting that combining a MEK inhibitor and a BRAF inhibitor could stave off cancer growth longer.

That new strategy is showing signs of success.

• In 77 patients who took a BRAF inhibitor (dabrafenib) and a MEK inhibitor (trametinib) made by GlaxoSmithKline, the drugs shrank tumors or delayed growth by 7.4 months on average. That’s not longer than what’s been reported for the BRAF inhibitor alone, however…
• The results were more encouraging for 24 patients who received the highest doses of the 2 drugs. Their tumors became stable or shrank and did not resume growing for 10.8 months on average.
• But, it’s too soon to know if the patients will live longer overall than they would have on a BRAF inhibitor alone. Even if they do, researchers expect that resistance will eventually develop.

The next step, says trial co-investigator Keith Flaherty of Massachusetts General Hospital, is to add a third drug to the cocktail, possibly matched to another genetic weak spot in the tumor: “We’re going to be in triplet territory pretty quickly.”

Adding drugs often increases toxicity, but the two-drug combo had an unusual side benefit: it reduced the occurrence of rashes and the growth of relatively benign skin tumors caused by a BRAF inhibitor alone.

The work was announced in a press conference yesterday, in advance of the annual meeting of the American Society of Clinical Oncology in Chicago in June.

[Via ScienceNOW, Bloomberg]

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