New drug improves progression-free survival, shrinks tumors in rare cancer for first time

June 1, 2013, Memorial Sloan-Kettering Cancer Center

The experimental drug selumetinib is the first targeted therapy to demonstrate significant clinical benefit for patients with metastatic uveal melanoma, according to new Memorial Sloan-Kettering Cancer Center research presented on Saturday, June 1, at the 49th annual meeting of the American Society of Clinical Oncology (ASCO).

The findings are potentially practice-changing for a historically "untreatable disease." Though uveal is rare—there are only 2,500 cases diagnosed in the United States each year—about half of patients will develop metastatic disease, and survival for patients with advanced disease has held steady at nine months to a year for decades.

Researchers found that progression-free survival (PFS) in patients receiving selumetinib was nearly 16 weeks and 50 percent of these patients experienced tumor shrinkage, with 15 percent achieving major shrinkage. Patients receiving temozolomide, the current standard chemotherapy, had seven weeks of PFS and no . Selumetinib also lengthened overall survival to 10.8 months versus 9.4 months with temozolomide, and side effects were manageable.

"This is the first study to show that a provides significant in a randomized fashion to advanced uveal melanoma patients, who have very limited treatment options," said Richard D. Carvajal, MD, a medical oncologist at Memorial Sloan-Kettering and lead author on the study. "This clinical benefit has never been demonstrated with other conventional or investigational agents, which is all we have been able to offer patients for decades."

Dr. Carvajal and his team decided to test selumetinib because it blocks the MEK protein, a key component of the tumor-driving MAPK pathway. This pathway is activated by mutations in the Gnaq and Gna11 genes, which occur in more than 85 percent of uveal melanoma patients; 84 percent of patients in this trial had one of the mutations.

Uveal melanoma does not respond to the drugs given to patients with melanoma on the skin; and, in fact, there is no drug approved specifically for treatment of the disease. Patients with uveal melanoma receive surgery to remove the tumor—and in some advanced cases, the entire eye—as well as radiation therapy or chemotherapy.

In the trial, researchers randomized 98 patients with metastatic uveal melanoma and administered selumetinib to 47, of which 81 percent had a Gnaq or Gna11 mutation. Of the 49 patients who received temozolomide, 86 percent had a mutation. Two patients were not treated. Despite the study's cross-over design—meaning patients whose tumors progressed on temozolomide could begin taking selumetinib—there was a trend towards improved survival with selumetinib. Selumetinib was generally tolerable, with most side effects manageable with conservative management or dose modification.

Dr. Carvajal is currently planning a confirmatory multi-center, randomized trial that will enroll approximately 100 and be led by Memorial Sloan-Kettering. "If we can confirm selumetinib's effectiveness in treating advanced uveal melanoma in this follow-up trial, it will become the standard therapy for this disease, forming a foundation for new drug combinations that could maximize selumetinib's MEK-inhibitor effect," he said. "It could offer a whole new way to treat this historically untreatable disease."

Explore further: Drug shown to reverse radioiodine resistance in some advanced thyroid cancers

Related Stories

Drug shown to reverse radioiodine resistance in some advanced thyroid cancers

February 14, 2013
The experimental drug selumetinib may allow some patients with advanced thyroid cancer to overcome resistance to radioiodine (RAI), the most effective therapy for the disease, according to new research from Memorial Sloan-Kettering ...

ASCO: combo antibody therapy effective for melanoma

May 17, 2013
(HealthDay)—Concurrent use of two immune checkpoint antibodies—ipilimumab and nivolumab—may be effective for the treatment of advanced melanoma, according to a proof-of-principal study presented in advance of the annual ...

Researchers report first success of targeted therapy in most common non-small cell lung cancer

November 28, 2012
A new study by an international team of investigators led by Dana-Farber Cancer Institute scientists is the first to demonstrate that chemotherapy and a new, targeted therapy work better in combination than chemotherapy alone ...

Study reports first success of targeted therapy in type of non-small cell lung cancer

May 31, 2012
A novel compound has become the first targeted therapy to benefit patients with the most common genetic subtype of lung cancer, an international clinical trial led by scientists at Dana-Farber Cancer Institute and other institutions ...

Study drug is first to help patients with recurrent low-grade ovarian cancer

February 8, 2013
Low-grade serous ovarian cancer is less common and aggressive than the high-grade variety, yet exceptionally difficult to treat when frontline therapy fails.

Recommended for you

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

These foods may up your odds for colon cancer

January 18, 2018
(HealthDay)—Chowing down on red meat, white bread and sugar-laden drinks might increase your long-term risk of colon cancer, a new study suggests.

The pill lowers ovarian cancer risk, even for smokers

January 18, 2018
(HealthDay)—It's known that use of the birth control pill is tied to lower odds for ovarian cancer, but new research shows the benefit extends to smokers or women who are obese.

Researchers develop swallowable test to detect pre-cancerous Barrett's esophagus

January 17, 2018
Investigators at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center have developed a simple, swallowable test for early detection of Barrett's esophagus that offers promise ...

Scientists zoom in to watch DNA code being read

January 17, 2018
Scientists have unveiled incredible images of how the DNA code is read and interpreted—revealing new detail about one of the fundamental processes of life.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.