Melanoma drugs extend life for some patients
Researchers will present studies of three promising new melanoma therapies today in Chicago.
Researchers will present studies of three promising melanoma therapies today, part of a wave of new treatments for the most aggressive forms of the disease.
None of the new therapies are cures for melanoma.
But a fraction of patients see rapid improvement in their condition, with dramatic shrinkage of their tumors, says F. Stephen Hodi, director of the melanoma center at Boston's Dana-Farber Cancer Institute.
Hodi, who studied a drug called ipilimumab, will discuss his findings in Chicago today at the annual meeting of the American Society of Clinical Oncology.
The Food and Drug Administration approved ipilumumab, sold under the brand name Yervoy, in 2011. Yervoy, the first new drug for melanoma to be approved in more than a decade, helped patients live a median of 10 months, four months longer than those who were given an alternative experimental therapy.
In a study of 245 melanoma patients, Hodi found that adding an immune stimulant, called GM-CSF, makes Yervoy even more effective.
About 68% of patients who received the combination therapy survived one year, compared with 51% of those given Yervoy alone, the study says.
Yervoy can sometimes overstimulate the immune system, causing serious or even life-threatening autoimmune problems, says Lynn Schuchter, a professor at the University of Pennsylvania School of Medicine who was not involved in this study.
Interestingly, adding the immune stimulant appears to reduce these complications, Hodi says, although these findings are still preliminary.
About half of patients taking either drug regimen experienced a major side effect. Among those taking the combination, the most serious complications included one heart attack and one case of a perforated colon.
Like a number of new melanoma drugs, Yervoy is considered an immunotherapy, because it aims to harness the power of the body's natural immune system to fight cancer, Hodi says.
The immune system is equipped to detect genetic mistakes in cancer cells and kill them, says Drew Pardoll, a professor at Baltimore's Johns Hopkins School of Medicine, who wasn't involved in the new study.
Cancers can often thrive, however, by "hijacking the immune system," Pardoll says.
Key soldiers in the immune system, called T-cells, normally kill cells and germs that look foreign. But T-cells also come with their own brakes. Without them, T-cells could go on constant attack, even targeting the body itself, causing autoimmune reactions.
Cancer cells can manipulate these brakes, by latching onto T-cells and preventing the body from fighting back.
Many new melanoma drugs are man-made antibodies designed to interrupt this process.
Some drugs target cancer cells, binding to proteins on their surfaces in ways that prevent tumors from interacting with T-cells.
Other therapies, such as Yervoy or a newer version, called nivolumab, attach themselves to the T-cells, protecting them from manipulation by tumors.
A new study of nivolumab, presented by Mario Sznol of the Yale Cancer Center, had promising early results.
Nivolumab shrank tumors in nearly 31% of patients, who lived a median of 17 months. Survival rates were relatively high for advanced melanoma that has spread to other organs, Sznol says.
About 61% of patients survived one year; 44% survived two years; 40% survived three years, the study says.
More than 80% of patients developed some sort of complication; 21% of these side effects were serious, the study says.
Pardoll says he's optimistic that these drugs have the potential to control tumors not just for a few months, but for a year or more.
"There are 10 or 12 pathways that tumors use to protect themselves from an immune attack," says Pardoll, noting that scientists may be able to develop drugs to block each of these paths.
So far, scientists have discovered only a handful of these defenses. Still, Pardoll notes, "we think there are other brakes that may be as or more important, and that they work together."
In another important development, scientists also published the results of a preliminary study on uveal melanoma, a rare cancer affecting the eyes, which is diagnosed in about 1,200 patients a year.
Advanced forms of the disease are difficult to treat, and chemotherapy is usually ineffective.
Treating the disease with an experimental drug from AstraZeneca, called selumetinib, helped patients live seven months longer than those taking chemotherapy.
Patients given selumetinib lived a median of nearly 12 months, while those given chemotherapy lived a median of almost five months, according to the preliminary study of 80 patients.
Although the study was very small, that survival advantage "is huge" for a disease this difficult, says Sandra Swain, president of the oncology society.
Michael Atkins, a melanoma specialist and deputy director of Washington's Georgetown Lombardi Comprehensive Cancer Center, said selumetinib is a major advance.
"This is the first time any systemic therapy has been shown to work in patients with ocular melanoma," Atkins said in a statement. "This disease has been viewed as practically untreatable until now."
Atkins notes that selumetinib blocks a protein called MEK, which helps send growth signals to cancer cells. These positive results were possible only because scientists did basic research to discover the critical gene mutations driving the disease, which differ from those involved in other kinds of melanoma.
The study "opens the door" for studying other drugs that block MEK, or combinations of them, Atkins said. Doctors should also consider testing this drug on patients with earlier-stage ocular melanoma, whose tumors have a high risk of spreading.
These drugs are all part of a sudden flurry of melanoma therapies, with more under development, says Timothy Turnham, executive director of the Melanoma Research Foundation.
The FDA has approved four new melanoma treatments in the past two years, with the latest two approved Wednesday.
Doctors will present 288 melanoma studies at the cancer conference over the next four days, compared with only 62 a decade ago.
Cathy Hershey, who lost her husband Matthew to melanoma three years ago, says the recent progress is encouraging. "I want to give hope to people," says Hershey, of Lincoln University, Pa.
USA TODAY interviewed Matthew Hershey in June 2010, during the annual cancer conference, about his experience with Yervoy, which was available then only through clinical trials.
At the time, he felt good, with few side effects. Taking the drug was difficult, mainly because previous rounds of chemo left his veins so battered that it was difficult for nurses to get a needle into them, she says.
Matthew had to stop taking Yervoy after only a few months, when his cancer spread to his brain. He died a few months later, in September, at the age of 43, leaving behind two girls, then ages 10 and 12.
When her husband was sick, Cathy Hershey did her best to educate herself about new treatment options, even attending the annual oncology meeting.
"As rough as treatment was, I do think it prolonged his life," says Hershey, who notes that her husband lived with cancer for five years. "When you have two young kids, if you can get to that one more soccer game, that's huge."
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