January 20, 2011

The New York Times

Drug to Fight Melanoma Prolonged Life in Trial

Advanced melanoma patients taking an experimental drug aimed at a particular mutation in their tumors lived longer than patients who did not receive the drug in a decisive clinical trial, the drug’s manufacturer, Roche, said Wednesday.

The results pave the way for Roche to seek approval to market the drug, which shrank tumors for an average of six months in earlier trials but had not yet been proven to prolong survival. Developed by Plexxikon, a small biotechnology company in Berkeley, Calif., it is based on an understanding of cancer’s most basic molecular workings that is seen as a potential key to providing more lasting treatments for melanoma and other cancers.
“In the past, with chemotherapy, we were grasping at things,” said Dr. Paul Chapman, an oncologist at Memorial Sloan-Kettering Cancer Center who led the trial. “Now we have a rational way of building on this. For the first time, we can see the path forward.”

About half of the 68,000 Americans who develop melanoma every year have a mutation in a gene, called B-RAF, that goes awry, for reasons not well understood, signaling cells to grow uncontrollably. The Roche drug works by blocking a malfunctioning protein the gene produces in cancer cells, but leaving the functioning proteins in noncancerous cells alone.

In the drug’s earliest trial, nearly every patient whose tumor cells contained the B-RAF mutation responded to the drug. That marked a radical difference from standard chemotherapies, whose reason for working in certain patients and not others is not well understood.

It also led some oncologists to assail the ethics of the trial, whose early results were disclosed on Wednesday, because it required some patients who might have been helped by the new drug to instead take a chemotherapy drug that was seen as essentially a placebo. Starting in January of last year, 338 patients were assigned to the chemotherapy arm of the trial, while another 338 received the Roche drug.

A series of articles in The New York Times last year described the early testing of the drug and the debate among oncologists over the design of the latest trial.

To measure whether the drug prolonged lives, the company was to compare survival on both arms of the trial. A Food and Drug Administration spokeswoman said Wednesday that the agency asked the company to perform that analysis sooner than originally planned. Patients on the chemotherapy arm of the trial will now be able to “cross over” and receive the drug.

Melanoma, the deadliest form of skin cancer, has been essentially untreatable after it spreads, with a median survival rate of eight months from the time of diagnosis. Roche has not yet reported how much longer patients taking its drug live, on average.

The company has opened an “expanded access” program at three cancer centers to provide the drug for melanoma patients who are not enrolled on the trial.

But even as patient advocates and oncologists welcomed the results of the Roche trial on Wednesday, they called for more expedient testing of drugs to combine with it. Research into why patients ultimately relapse after responding to the drug is pointing to other drugs similarly tailored to particular mutations that could yield more durable benefits for patients.

“Combining drugs is where the future of oncology treatment lies,” said Timothy Turnham, executive director of the Melanoma Research Foundation, a nonprofit advocacy group. “We need companies to cooperate and make this happen now.”