UCSF trial offers new hope for melanoma patients

University of California San Francisco successfully tests new, highly effective drug treatment

Shannon Jimerson, an advanced-stage melanoma patient being treated at UCSF, did a little dance this week while still sitting on the exam table after she got the news she desperately wanted to hear.

Nine months after starting a combination drug therapy in early-phase clinical trials, her tumors were continuing to shrink.

“You have very minimal disease left,” said Dr. Alain Algazi, a skin cancer specialist.

Algazi told her that her tumors had shrunk by 85 percent, leaving her with just a few “lousy little tumors” he hoped the drugs would continue to target.

Jimerson, 34, of Fairfield has benefited since January from a growing body of research that is giving new hope to patients with melanoma, the most deadly form of skin cancer. Melanoma is diagnosed in about 68,000 Americans annually and kills more than 8,700 each year.

Before entering the trial, Jimerson wasn’t sure she’d be alive at this point. Her body had become so riddled with tumors that she was afraid to lay a hand on her own skin for fear she’d find a new lump. She did find a new spot, on her shoulder, and was scheduled for a biopsy two weeks after she started taking the investigational drugs.

“But by the time I got there, there was nothing to biopsy,” said Jimerson, the mother of two young daughters and children’s pastor at her church. “It was absolutely a miracle, this drug.”

The combination of the two oral drugs, both being developed by GlaxoSmithKline, are designed for people who have a genetic mutation that is found in about half of all melanoma cases. The drugs target two different points along a pathway the cancer uses to proliferate.

At least half and up to as many as 77 percent of 71 patients in the earliest phase of the trial experienced reductions in tumor size by a third or greater, researchers said. The company is seeking to enroll about 280 patients in second-phase studies and is already planning for third-phase trials.

The results are promising considering most of the current therapies for melanoma have been found to work in fewer than 20 percent of patients, and often have far lower levels of effectiveness.

“This is definitely a great moment for patients with melanoma,” said Kiran Patel, GlaxoSmithKline’s director of oncology research and development. “Our goal is to progress science and really bring new and better options for patients.”

Patel said he could not estimate when the company will seek federal approval for the drug combination. “We remain enthusiastic about targeted approaches and will keep doing the right studies so we can get those answers,” he said.

Until this year, the last drug approved for melanoma was in 1998. But in August, the U.S. Food & Drug Administration fast-tracked the approval of a drug from South San Francisco’s Genentech Inc. called Zelboraf, which targets and inhibits the genetic mutation known as BRAF V600E. The GlaxoSmithKline drugs work on that same pathway, but also targets a second point on the path.

“We haven’t had any real breakthroughs since the mid ’90s, and now it’s like every few months we have something exciting,” said Dr. Adil Daud, director of UCSF’s Melanoma Program and chief investigator of the trial.

Scientists discovered that when the protein BRAF is mutated, it can become hyperactive and cause cells to grow out of control. The Genentech drug was found to work in about 50 percent of late-stage melanoma patients with the mutation.

While researchers found the results astounding, especially considering that they previously had little to offer people with metastatic melanoma, they quickly realized that the disease started progressing in some patients after several months on the drug. They suspected the cancer was finding a “work-around” in some cases by using a pathway regulated by another protein called MEK.

The GlaxoSmithKline trial drugs Jimerson has been on since January go after both BRAF and MEK. Genentech, for its part, is in clinical trials for its own combination therapy using Zelboraf, its already-approved BRAF inhibitor, and a MEK inhibitor the company is developing. UCSF is involved in that trial as well.

The hope is that patients will be able to stay disease-free longer on a drug that blocks the cancer’s pathway in two places rather than just one.

“It’s like a river being blocked by two dams,” UCSF’s Daud explained. “Maybe you’ll overflow the first dam, but then the other part will take over.”

Daud’s colleague, Algazi, said researchers have the challenge of figuring out what other pathways exist and what drugs can be created to fend off those new routes to give the disease a “long-term, knock-out punch.”

For Jimerson — who has experienced few side effects other than a mild rash, some fatigue and an occasional fever — the trial means she has hope for the future.

“It allows me to live my life,” she said. “My kids know I have cancer, but cancer isn’t the focal point of our lives.”

1 Comment
Anonymous over 11 years ago

This is a wonderful articule about the recent developments in potentially powerful therapies for melanoma. However, Yervoy (ipilimumab), a drug produced by Bristol-Myers Squibb for metastatic melanoma, was FDA-approved in March of this year, just before Zelboraf was approved.