Experimental targeted cancer drug helps 4 out of 5 metastatic melanoma patients [Updated]

An experimental anticancer drug that targets a specific genetic mutation benefits 80% of patients with metastatic melanoma, although in some cases the benefit was short-lived, researchers said Wednesday. The results came in a relatively small Phase II clinical trial, and testing will now proceed to a larger Phase III trial to gain approval for marketing the drug, called PLX4032. Researchers hope the drug might also provide benefits for some other types of tumors that share the same genetic defect.

Early-stage melanoma is normally successfully treated by surgical removal of the tumor, but once it has metastasized, the outlook is generally much more grim. The two drugs approved for treating it, interleukin-2 and dacarbazine, provide benefits in fewer than 20% of patients. For those with metastatic melanoma, the prognosis for survival is currently about nine months or less, with 9,000 people dying of it in the U.S. each year.

PLX4032 is targeted against a gene and a protein, both called BRAF, that stimulate growth of tumor cells. About half of melanoma patients have a mutated form of the gene that does not shut off, so that BRAF is continually produced, driving tumor growth. PLX4032, developed by Plexxikon Inc. of Berkeley and licensed to Roche Pharmaceuticals, blocks the action of BRAF and thus slows or prevents growth.

Dr. Keith Flaherty of Massachusetts General Hospital in Boston, Dr. Paul Chapman of the Memorial Sloan-Kettering Cancer Center in New York and their colleagues enrolled 32 patients with metastatic melanoma and the BRAF mutation. Patients received the drug orally twice a day. In 26 of those patients, the researchers reported in the New England Journal of Medicine, the tumors shrank more than 30% and another two had some reduction in the size of their tumors. In two of the patients, the tumors disappeared completely. The tumor cells eventually developed resistance to the drug, but the patients received an average progression-free survival of eight months.

One patient it did help was Shirley Taylor Chance, a 66-year-old foreclosure specialist from Lake Elsinore. Last summer, she was suffering frequent headaches, which she attributed to her high blood pressure and propensity for migraines. But on Sept. 25, a “horrendous headache” prompted her to seek help in the emergency room. The next morning, the neurologist came back to her and told her she had metastatic melanoma that had spread to her brain and elsewhere. He said that she had two to six months to live. Her son was a friend of Dr. Robert Gale and urged her to send him her medical records. She did, and he suggested that she contact Dr. Antoni Ribas at UCLA’s Jonsson Comprehensive Cancer Center. “He put me on another drug that didn’t work, and by Christmas I had tumors popping out of my body where I could feel them,” Chance said.

She joined the clinical trial for PLX4032 in March. “Almost immediately, I got a real high, and was feeling really really good,” she said. Her last four CT scans have all showed continued shrinkage of the tumors in her body, and the last two MRIs have shown shrinkage of those in her brain as well. She was around for the birth of her grandson, which she hadn’t expected to be. “I used to wake up every day dying,” she said. “Now I wake up living.”

In a statement, Flaherty said: “We’ve never had a credible first treatment option for metastatic melanoma, so this has completely transformed how we approach treatment for patients with the BRAF mutation. Although we don’t know how long response may last, the ability to beat this disease down in the short term will buy us time to strategize second-line therapies and design the next generation of trials.”

Patients interested in enrolling in trials at UCLA should call (888) 798-0719.

[Updated: Aug. 27, 10:50 am. The reported results were not from a Phase II trial. They were from the second stage of a Phase I trial to test safety.]

-- Thomas H. Maugh II / Los Angeles Times