AstraZeneca's selumetinib looks promising for rare cases of eye melanoma

CHICAGO--One of the big trends on display at ASCO this year has been the dissection of the cancer field. As investigators narrow their search for effective remedies for more narrowly defined patient populations, clinical trials in oncology have sometimes begun to look more like the investigative work you find in the rare-disease arena. And nowhere was that more evident than in a presentation that was given on the efficacy of AstraZeneca's ($AZN) selumetinib for rare cases of advanced melanoma in the eye.

Richard Carvajal, an investigator at Memorial Sloan-Kettering Cancer Center, says that in a clinical study the selumetinib arm more than doubled progression-free survival in patients, jumping from 7 weeks in the chemotherapy arm of the study to 15.9 weeks in the drug arm. Overall survival was 9.4 months for chemo to 10.8 months in the selumetinib group, with crossovers into the drug arm perhaps explaining the slim OS benefit that was tracked.

This is the first experimental drug to show evidence of efficacy in a clinical trial, says Carvajal, noting that of 8 previous studies with a total of 157 patients, only two people experienced a significant reduction of their tumors. In this Phase II study half of the patients saw their tumors shrink, with 15% seeing a major reduction. There are about 2,000 new cases of uveal melanoma diagnosed every year in the U.S.

Investigators stumbled onto this indication as they studied the disease pathway. Close to 9 out of every 10 patients with uveal melanoma have Gnaq or Gna11 alterations that activate the MAPK pathway. Selumetinib inhibits MEK, which the investigators say is a key component of the MAPK pathway. Stop the MEK protein and you could stymie growth of the cancer cells, they theorized, correctly as it turned out. 

While no breakthrough, the data do indicate that selumetinib has a solid shot at becoming the first approved therapy for melanoma of the eye, putting it on track to become the standard of care. And Carvajal also notes that it points down the pipeline, to new studies that can test this drug in combination with others in search of better results. 

"Finally, something is having some kind of impact, and you can build on that," Tim Turnham, executive director of the Melanoma Research Foundation, tells Reuters.

AstraZeneca in-licensed selumetinib from Array BioPharma ($ARRY) about a decade ago, and development hasn't been easy. In the fall of 2011 the company reported that the therapy had failed a study for lung cancer patients with KRAS mutations. The drug is currently being studied for a number of cancer indications, with AstraZeneca insisting that the Phase III therapy is one of its brightest late-stage prospects.

- here's the story from Reuters