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Advances in melanoma treatment prolonging lives

Melanoma patient Richard Murphy and his wife, Lori, at home in Marshfield with children Jake, 12, Max,14, and Mackenzie, 9. Murphy was diagnosed in 2008.

John Tlumacki/Globe Staff

Melanoma patient Richard Murphy and his wife, Lori, at home in Marshfield with children Jake, 12, Max,14, and Mackenzie, 9. Murphy was diagnosed in 2008.

Richard Murphy is both the unluckiest and luckiest of men.

The former hotel and restaurant owner was unlucky when he developed an unusual type of a rare skin cancer that strikes only about 500 Americans a year. By the time doctors caught it, it had spread beyond the tumor in his nose.

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When Murphy, who lives in Marshfield, was diagnosed, doctors had only three treatments to choose from for stage 4 melanomas like his, none of which had been shown to extend lives. Only four in 25 patients survived five years.

But he was lucky enough to be diagnosed in 2008.

Surgery bought him enough time to make it to 2010, when an incredible transformation of melanoma care began.

Since then, four new treatments for advanced melanoma have won federal approval, another two are likely to be approved by the fall, and a few more are working their way through the process.

New studies to be released at a cancer research conference beginning this weekend in Chicago are expected to offer more good news.

Doctors, normally hesitant to use the word “cure,” are starting to lose their reserve.

“Someone with metastatic melanoma, I used to tell them to ‘eat whatever you want.’ Now, I’m saying ‘you should watch that cholesterol,’ ’’ said Dr. Patrick Hwu, chairman of the Department of Melanoma Medical Oncology at the University of Texas MD Anderson Cancer Center in Houston.

Murphy, 48, who once worried that he wouldn’t live to see his youngest graduate from kindergarten, is daring to dream about attending her grade-school graduation — even her wedding.

“It’s crazy. It’s been absolutely crazy. We’ve had a helluva ride since ’08,” he said.

This seismic shift in melanoma care — largely brought about by enlisting the immune system in the fight — might eventually be used to treat other cancers, researchers said. Smoking-related lung cancers, among others, are now starting to respond to similar treatments, according to research to be presented at this week’s conference.

“We really are in a historical time right now,” said Dr. F. Stephen Hodi, director of the Melanoma Treatment Center at the Dana-Farber Cancer Institute. “Cancer treatment five years ago compared to five years from now — it’s going to be completely different.”

The payoff has come from decades of basic research that led to a deeper understanding of the genetics of cancer and how tumors interact with a patient’s immune system.

In many cancers there are now so-called targeted therapies, designed to attack tumors that have specific genetic mutations. A large percentage of advanced melanomas have mutations in a gene called BRAF, which is involved in cell growth, division, communication, and death.

Medications that turn down this gene’s activity have shown near-miraculous short-term results for patients with melanoma. Tumors have melted away in weeks.

But even when combined with a second targeted therapy that attacks a different spot along the same genetic pathway, the tumors usually grow back in under a year — and then may be more aggressive, said Dr. Antoni Ribas, a professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles.

Immune therapies, which work by trying to spur the body to fight off the cancer by itself, offer the promise of controlling a cancer long-term, but so far help a smaller percentage of patients than targeted therapies.

Scientists have long known that melanoma and kidney cancer were particularly vulnerable to a strong immune system. There have been extremely rare cases when someone’s melanoma miraculously disappeared on its own, said Dr. Steven A. Rosenberg, chief of the surgery branch of the National Cancer Institute.

In a major breakthrough in the 1980s, Rosenberg discovered that a drug called Interleukin-2 boosts the immune system of about 7 percent of melanoma patients enough to allow their bodies to fight off the cancer. One of the first melanoma patients he treated with Interleukin-2 in 1985 is still alive and well.

But it wasn’t until 2010 that researchers found another drug that could do the same thing for more people. That drug, called ipilimumab (sold commercially by Bristol-Myers Squibb under the name Yervoy) seems to boost the immune system, so that some people’s bodies can identify and kill cancer cells on their own.

The next class of drugs — called PD-1 inhibitors — seems to fight advanced melanoma better, early studies suggest, and might work for even more people in combination with Yervoy.

And yet another generation of drugs is finishing up early trials, some of which will be reported within the next week, Hodi said.

Murphy has been through nearly every treatment on the list. In the first two years after his diagnosis, he had surgery (twice), radiation (also twice), and chemotherapy, before he ran out of conventional therapies.

When his tumors came back, Hodi, his doctor, put him on Yervoy, which had not yet been approved by the Food and Drug Administration. His results looked great at first, but three months later his tumors had grown back. From August to December of 2011, Hodi used radiation to keep the tumors from growing too much.

Then in March 2012, Murphy started another experimental drug, MK3475, one of the PD-1 inhibitors. It seemed to be doing little. In May he was hospitalized when his kidneys reacted badly and Hodi pulled him off the drug. In June his scans looked clear of cancer, surprising everyone, and they’ve remained that way ever since.

“I was at a funeral the other day and bumped into my aunt. She says, ‘Are you cured?’” Murphy said. “I’ll never use that word. But I certainly am in a good spot.”

Short of curing cancer, doctors have always hoped to get enough effective medicines to keep patients alive, moving on to the next drug when one is no longer effective.

Many melanoma patients, like Murphy, are there now, with each drug keeping them going for at least another year, said Ribas.

“We haven’t hit a home run yet, but we’ve had several things that are making this into a chronic condition as opposed to something that’s deadly within a few months,” Ribas said.

As exciting as the new treatments are, the advances need to keep coming, Hwu said.

“Every day we still have patients that have had everything and we still have to send them to hospice,” he said.

Still to figure out, Hwu and others said: Who will benefit from which therapy; how to get new drugs to more patients faster; how to save everyone — not just the lucky ones.

Cost issues need to be worked out as well. A four-treatment course of Yervoy costs $120,000, and now researchers are suggesting that it may need to be combined with at least one other drug, likely to cost around the same amount.

Doctors argue that the treatment is cost-effective if it can add years or even decades to someone’s life, but no one has figured out how a country that is already worried about the cost of medical care will be able to afford these combination therapies.

Money is also an issue for researchers, like Hodi, Hwu, and Ribas, who say they could come up with more therapies faster if they didn’t have to spend so much of their time hunting for grants.

It’s crucial to keep making innovations, Hwu said, both for patients like Murphy and for the metastatic melanoma patients who will be diagnosed in the future, so that none die as a result of their diagnosis. “Which I think is a possibility in the near future,” Hwu said. “We need to really work hard to move the bar ahead.”

Karen Weintraub can be reached at weintraubkaren@gmail.com.
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