* AstraZeneca drug helps delay tumor growth
* New studies planned for rare eye cancer
By Julie Steenhuysen
CHICAGO, June 1 (Reuters) - In his first few weeks as head of the melanoma group at Memorial Sloan-Kettering Cancer Center seven years ago, a young man walked into Dr. Gary Schwartz’s office with a rare form of the skin cancer that affects the eye.
“It was horrible. He died of metastatic disease. He was only 24. I promised him I would find a way to cure his cancer,” recalls the physician-scientist of the patient who helped inspire his quest to find an effective treatment for uveal melanoma, which affects 2,000 to 3,000 patients each year.
Researchers from Memorial-Sloan Kettering on Saturday reported results of the first clinical trial ever to show that a drug helped patients with advanced uveal melanoma at the American Society of Clinical Oncology Meeting in Chicago.
The mid-stage clinical trial led by Dr. Richard Carvajal, Schwartz’s colleague, found that an experimental drug from AstraZeneca called selumetinib shrank tumors in half of all treated patients and doubled progression-free survival, a measurement of the amount of time a medicine controls cancer before it starts to grow again.
“This represents the first real victory in medical oncology for patients with uveal melanoma,” said Schwartz, who is chief of the New York hospital’s melanoma and sarcoma service.
Melanoma of the eye is far different from other forms of the deadly skin cancer, and attempts to treat it in the past have largely failed. Out of a total of 157 patients treated in eight different prior clinical trials, only two patients had significant tumor shrinkage.
Like skin melanoma, uveal melanoma is caused by specialized, pigment cells called melanocytes, but biologically it is “completely distinct from skin melanoma,” Carvajal said in a telephone interview. “Nothing has ever been shown to help patients with metastatic uveal melanoma before,” he said.
Most patients are diagnosed with early stage disease, and treatments range from radiation and surgery to remove the tumor to full removal of the eye. In spite of these efforts, the disease spreads to other organs in about half of patients, giving them an expected survival of nine to 12 months.
About 90 percent of patients with this cancer have mutations in genes called Gnaq and Gna11. Through work in Schwartz’s lab, researchers discovered that these mutations trigger a known cancer pathway called MAP kinase that helps feed the cancer.
Schwartz and Carvajal began looking for ways to shut down this growth driver using drugs under development that block different aspects of this pathway. Selumetinib, which blocks a protein called MEK, appeared to work.
“We showed if you take a cell with the mutation and drop this drug in there, you can actually prevent the cell from growing,” Schwartz said.
But would it work in people?
After several attempts to gain funding for a clinical trial, Schwartz and colleagues won a grant from the National Cancer Institute through a program that makes drugs available for testing.
But that still left it up to Schwartz, Carvajal and colleagues to raise the more than $1 million to pay for the cost of running the clinical trial. For this, they turned to a fundraising program called Cycle for Survival that supports research on rare cancers and was started by one of Schwartz’s former patients.
For the clinical trial, the researchers enrolled 98 patients with advanced melanoma of the eye. About half of the patients got selumetinib and the other half got temozolomide or Temodar, a standard chemotherapy that is used in skin melanoma. Patients whose tumors got worse on the chemotherapy were given the option of crossing over to the selumetinib arm of the study.
Half of the patients treated with selumetinib had tumor shrinkage, with 15 percent achieving major tumor shrinkage, compared with no tumor shrinkage in the chemotherapy group.
The average time it took for the disease to progress was 15.9 weeks in the selumetinib-treated patients, compared with seven weeks in the temozolomide arm.
Tim Turnham, executive director of the Melanoma Research Foundation, said the results are encouraging in a group of patients who have no other options. “Finally, something is having some kind of impact, and you can build on that,” he said.
The research is still early, and it may be years before a treatment becomes commercially available. But Carvajal said he hopes patients can benefit from clinical trials until then.
The team is working with AstraZeneca on plans for a follow-up study to confirm the findings for selumetinib, which the company has been studying as a treatment thyroid and lung cancer. That study will open this fall.
And they are also working with GlaxoSmithKline and the National Cancer Institute to study their MEK inhibitor, called Mekinist, or trametinib, which won approval this week for treatment of advanced melanoma.
The team wants to combine Mekinist with an experimental Glaxo treatment that blocks a different protein called Akt based on studies in Schwartz’s lab that show the combination may be even more effective at halting tumor growth.