When hope returns: a new drug takes on a rare, aggressive skin cancer

"It's working," Fred Ewart's oncologist told him and his family a month ago.

Not many people have survived the rare type of skin cancer afflicting the 83-year-old retired school teacher.

Last August, Ewart was diagnosed with Merkel cell carcinoma, a very aggressivecancer that kills one of every two peoplediagnosed with it. If the diseasemetastasizesspreads beyond the skin and lymph nodes the average lifespan is just nine months from the time ofdiagnosis. Only one in five patients lives longerthan five years.

Patients are usually treated with chemotherapy, but if there is any benefitit is usually short-lived.

That's what happened toEwart. Merkel tumours showed up on his back in August;just onemonth later he learned the cancer had spread to his liver. He was given two chemotherapy drugs at Princess Margaret Hospital in Toronto, which worked initially, but then the cancerprogressed again.

There were clinical trials for treatments that might have helped, but Ewart's liver was no longer in good enough shape to allow him to participate.

New drugs and new hopes

Those clinical trials were testing a newer type of treatment calledimmunotherapy, which usesthe body's own immune system to fight disease.

Findings from one trial for a drug called avelumabwere presented earlier this month at the American Society of Clinical Oncology (ASCO)meeting in Chicago, the country's largest annual oncology conference. The trial's lead investigator, Dr. HowardKaufman, called the results"a potential breakthrough" forMerkelpatients.

Avelumabhad an objective response a measurable decrease in tumour sizefor 28 of the 88 patients withmetastasizedMerkelcell carcinoma.For eightof those patients,tumours could no longer be detected at all.

Astudypublished in the New England Journal of Medicine in Aprilreported that 14 of25 patients had an objective response to the drug, and four of them had a complete responsenearly twice as high as the responsetoavelumab.

Patients in the avelumabstudyhad already tried chemotherapy,which can suppress the immune system,while those in thepembrolizumabtrial had not,whichmay explain why that drugproduced a better response.

Merck, the drug's manufacturer, recently received two approvals from Health Canada for pembrolizumab to treat metastasized cancer:in April, conditionally, for non-small cell lung cancer, and in late May for melanoma. Merck has not yet filed for approval to use it for Merkel cell carcinoma.

Whenthey work, both of these newimmunotherapydrugs essentially take the brakes off of cancer-fightingT-cells:white blood cells that are part of the body's immune system andcan sometimes be tricked into thinking thatcancer cells are normal.

'Dad doesn't have a choice, so give it to him'

Once chemotherapy had stopped working for Ewart, his oncologist suggested that he could take avelumabor pembrolizumab except that there was no way to get him access tothe drugs through the Canadian health care system.

Canada is one of the countries with "the most restricted access to publiclyfunded cancer drugs," compared to 12 other industrializednations,a2012 studyfound.

Two weeks ago, the Canadian Health Policy Institute published a report by pharmacoepidemiologist Nigel Rawson, which looked at approval patterns for cancer drugs.Rawsonfound:

• Median review time was nine months in the U.S. and 13 months in Canada.
• One-third of cancer drugs were submitted for review to the U.S.Food and Drug Administration six months before they were submittedto HealthCanada.
• Once a new drug is approved, Canadians wait months longer for reimbursement compared to Americans, and patients in some provinceswait twice as long as those in others.

"The estimated number of patients potentially negatively impacted by delayed access in [Canada], and the associated economic costs are huge," the study concluded.

Rawsonsays Health Canada shouldexplain why it takes such a long time to review new drugs. While it may be hampered byresource constraints, hesays"it's incumbent on them to say, 'if we can't afford it, we can't afford it and these are the reasons why.'"

Ewart'sfamily says he has been adversely affected by Canada's slow drug approval process. "If someone gives his permission and knows the risks, I don't see why it shouldn't be available," his daughter Jane says.

"We're really risk averse here," her sister Margaret adds.

While she recognizes that drug trials are supposed to determine whether a drug does more good than harm, Margaret says, "Dad doesn't have a choice, so give it to him."

However, a great many medical treatments that begin with great promise are later abandoned. For example,Avastin, once the best-selling cancer drug in the world, had its approval for treating breast cancerwithdrawn in the U.S. and Canadain 2011.

• Medical spin is a widespread problem

A2014 New England Journal of Medicine articlefound that"early access and shortened development and review times have also been associated with negative public health outcomes," adding that "data collected with the use of early-stage clinical-trial methods are unstable and may be subsequently disproved in larger, morerigorous trials."

Life and death decisions

With neither avelumabnor pembrolizumab approved for Merkel cell carcinoma in Canada, and running out of time to get the drug on compassionate grounds which hisoncologist, Marcus Butler, was pursuingEwart decided to pay for pembrolizumab himself.

In the U.S., pembrolizumab costs upwards of about $6,700 US per dose, according to comparison shopping websiteGoodRx.com. It is administered by injection approximately every three weeks; a full course of treatment generally lasts for about one year.

Ewart had his first injectionin lateApril, at the private Bayshore Clinic north of Toronto. Theprice tag:$7,700.

A few weeks later, Ewart and his family went to see his oncologist. According to son John, Butler walked in with a smile on his face. He saw that Fred's skin hadimproved and that he was inbetter shape;he had also already seen bloodwork results.

"He looked at my dad and gave him a big hug, and Dr. Butler started to cry, and of course we all started to cry, and Butler said, 'It's working, it's working.'"

Jane added that her father"had been a frail fraction of himself before this miracle drug, and it's just amazing, and I wish other people would have this opportunity."

New cancer drugs cost $120,000 a year

But then there's the cost. "It's insane, it's crazy for people to say either I'm going to die or I'm going to somehow fork over $7,700," says Jane.

Pembrolizumab's price is pretty much average for a new cancer drug today.

"In 2014, all new U.S. FDAapproved cancer drugs were priced above $120,000 per year of use," Hagop Kantarjian of the M. D. Anderson Cancer Center and Ayalew Tefferi of the Mayo Clinic wrote in 2015.

They also foundthe average price of new cancer drugs in the U.S. was five to 10times higher in 2012 than 15 years earlier.

Estimating that pharmaceutical companies have profit margins of 20 to30 per cent, they wonder whether current pricing is merely based on what the market will bear.

On June 9, the Ewarts received more good news. Butler told them Merckwill begin providing Fred with pembrolizumab (brand name Keytruda) for free, on compassionate grounds.

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