Are We Winning the Fight Against Melanoma?

Medically Reviewed by Brunilda Nazario, MD on January 11, 2016
From the WebMD Archives

Jan. 11, 2016 -- When former President Jimmy Carter announced late last year that his advanced melanoma appeared to be in remission, family and followers of the 91-year-old humanitarian were overjoyed.

Some said it seemed nothing short of a miracle, since the skin cancer is often deadly in its advanced form. His doctors, though, pointed to one of the drugs prescribed to Carter as a major reason for his improvement.

Among other treatments, Carter took pembrolizumab (Keytruda), one of several new meds approved in the last 4 years by the FDA to treat melanoma. This explosion of new drug approvals in such a short time came after decades of stalled progress and glum outlooks for many diagnosed in advanced stages of this deadly cancer.

About 73,000 new cases of melanoma were expected in 2015, with about 10,000 deaths, according to the American Cancer Society.

Experts are hopeful the new drugs that have received the FDA's OK since 2011may change those death statistics. The meds fall into two categories. Immunotherapy treatments prime the immune system to fight the cancer. Targeted therapies take aim at common genetic mutations found in a small group of melanoma patients.

"Talk about game-changing," says Len Lichtenfeld, MD, deputy chief medical officer for the American Cancer Society. "All of a sudden you have researchers talking about half the patients getting benefits [for some of the drugs]." In years past, doctors gave people with advanced melanoma much less hope.

"These are incredible advances," Lichtenfeld says. "We now have something to offer where we had nothing."

The new drugs, for the most part, are only approved for stage IV melanoma or advanced disease, says Joseph Skitzki, MD, an associate professor of surgical oncology at Roswell Park Cancer Institute. Stage IV cancer means it has spread to other organs or parts of the body -- in Carter’s case, his brain.

When doctors spot melanoma early, removing it surgically produces a cure rate of 97% to 100%, Skitzki says.

But even with the new ''wonder'' drugs for advanced melanoma, the war isn't won, Skitzki and other experts say. The new medications don't work for everyone, and many unanswered questions remain. 

"We aren't even certain" how long the benefits of the drugs will last for patients, Lichtenfeld says. "We are still very much learning" who the meds will help.

The drugs also come with breathtaking costs. The average Medicare patient will pay $60,000 of the $300,000 yearly costs for treatment with one combination of drugs. For other meds, experts predict annual costs could approach $1 million per patient.

Focus on the New Drugs

The new immunotherapy meds for melanoma approved include:

  • Ipilimumab (Yervoy)
  • Nivolumab (Opdivo)
  • Peg interferon alfa-2b (Sylatron)
  • Pembrolizumab (Keytruda)
  • Talimogene laherparepvec (Imlygic, T-VEC)

Keytruda, Opdivo, and Yervoy are called "checkpoint inhibitors" because they take the brakes off the immune system, allowing it to fight the cancer. Imlygic uses a virus to help tumor cells to destruct, triggering an immune system response against the cancer.

Targeted therapies recently OK'd include:

  • Cobimetinib (Cotellic) in combination with vemurafenib
  • Dabrafenib (Tafinlar)
  • Trametinib (Mekinist)
  • Vemurafenib (Zelboraf)

Targeted treatments go into the cell and shut it down, says Tim Turnham, PhD, executive director of the Melanoma Research Foundation. These treatments target genetic mutations found in some melanoma patients.

New Meds: How Effective?

That depends on the individual and the drugs.

With some of the new meds, about 40% of patients benefit, Skitzki says. That’s a far higher percentage than with standard chemotherapy drugs of the past, which helped about 10% or fewer of the people who took them. He says that 34% of patients responded to Keytruda in clinical trials, for example. Some people go into remission.

Of course, many with advanced disease don't improve after taking the drugs, Skitzki and others say. "Overall," Skitzki says, "we're not winning but war, but we are definitely winning the battle."

For instance, a combination of ipilimumab and nivolumab kept patients alive without the disease getting worse for a median of 11.5 months (half longer, half less) for melanoma that had spread, researchers reported at the 2015 annual meeting of the American Society of Clinical Oncology. That's considered remarkable for a disease viewed as almost untreatable 5 years ago, says Leonard Saltz, MD, chair of the pharmacy and therapeutics committee at Memorial Sloan Kettering Cancer Center.

Another new drug, Imlygic, a modified herpes virus, treats melanoma lesions that can't be removed entirely by surgery. The drug is injected directly into the melanoma lesion. It makes copies of itself inside the cancer cells and causes them to rupture and die. After 6 months of treatment, about 16% of 436 patients had a decrease in the size of skin and lymph node lesions that lasted for at least 6 months, compared to just 2% of patients getting a comparison treatment.

But studies haven't shown that the drug improves overall survival, the FDA says. Nor have researchers found it to have an effect on melanoma that has spread to the lungs, liver, bone, brain, or other internal organs. And like all drugs, it has potential side effects, including flu-like symptoms. And people on it can get a herpes virus infection, according to the FDA. Other experts say they haven't seen any such infections, though.

People can become resistant to immunotherapy drugs, Turnham says, but experts are just beginning to study resistance. Meanwhile, if targeted treatment fails to work for some patients, they often see the cancer spread rapidly, he says. But it's not clear whether this is simply the natural course of the disease or something related to the treatment. "It may well be that the targeted therapies are holding progression in check and when they fail, the disease essentially makes up for lost time."

It's too early to say which of the new drugs looks most promising in terms of extending lives, Turnham says. But he thinks the strongest contenders will be either Keytruda and Opdivo or a combination of the targeted therapy drugs. 

"If you compare 2- and 3-year survival rates of immunotherapy and targeted therapy, the results are fairly similar," Turnham says. But ''the general feeling, though, is that immunotherapy will have a longer response time. We just don't have the data yet." (Most tumors shrink with treatment -- response time measures tumor shrinkage in response to treatment and how long that shrinkage lasts.)

The Price Tags

Costs are a major concern, both for doctors and patients.

All of the drugs for advanced disease are expensive, Turnham says. The overall cost before insurance varies by whether the drug is given as a limited course of treatment or indefinitely, until it no longer helps someone.

"Yervoy is about $30,000 per infusion, and the course of treatment is four infusions," Turnham says. "Zelboraf is about $11,000 a month, and you keep taking it until it no longer works."

Assistance programs offered by drug companies can help. But many experts, including Saltz of Memorial Sloan Kettering, worry about how long society will be able to sustain the sky-high costs.

"We've had a tendency to think price is someone else's problem," Saltz says. "No, it's everyone's problem." In an editorial published in October in JAMA Oncology, he notes that the price for a month of cancer treatment in 1970 was about $170 per person. "By 2014, we were looking at $10,000 a month," he writes.


Others experts point out that the drugs already have widespread benefits. Keytruda is approved to treat lung cancer. Opdivo is OK'd for both lung and kidney cancer in addition to melanoma.

Even so, as a society we need to figure out what we can afford on an individual patient basis, Saltz says.

"If we had a drug that prolonged life by a month and it cost $1 billion per patient," he writes, ''we would all say, 'That's too much... we won't use it.' If we had a drug that prolonged life by 5 years and cost $100 per patient, we would say, 'That's wonderful... put it in the water supply.'''

According to Saltz, there is a tipping point, and we must be willing to search for that. That effort will require input from doctors, patients, pharmaceutical and biotech companies, he says, along with insurers and the government.

Show Sources


JAMA Oncology, October 22, 2015 online.

Leonard Saltz, MD, professor of medicine, Weill Cornell Medical College and chair of the pharmacy and therapeutics committee, Memorial Sloan Kettering Cancer Center..

Joseph Skitzki, MD, surgical oncologist and associate professor of surgical oncology, Roswell Park Cancer Institute.

Tim Turnham, PhD, executive director of the Melanoma Research Foundation.

Len Lichtenfeld, MD, deputy chief medical officer, American Cancer Society.

FDA press releases.

American Cancer Society.

Cancer Research Institute: Melanoma.

Kristen Davis, spokesperson, Amgen.

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