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

Fred Ewart is taking a new immunotherapy drug in the hopes it will help him survive Merkel cell carcinoma. So far, it's working.

Chemotherapy didn't work for Fred Ewart, but immunotherapy is helping

Fred Ewart and grandchildren Elsa Johnston and Matthew Strong cut a birthday cake last year. Ewart, a retired school teacher, is now 83. (Supplied by Ewart family)

"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 aggressive cancer that kills one of every two people diagnosed with it. If the disease metastasizes — spreads beyond the skin and lymph nodes — the average lifespan is just nine months from the time of diagnosis. Only one in five patients lives longer than five years.

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

That's what happened to Ewart. Merkel tumours showed up on his back in August; just one month 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 cancer progressed 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 called immunotherapy, which uses the body's own immune system to fight disease.

Findings from one trial for a drug called avelumab were 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. Howard Kaufman, called the results "a potential breakthrough" for Merkel patients.

Avelumab had an objective response — a measurable decrease in tumour size — for 28 of the 88 patients with metastasized Merkel cell carcinoma. For eight of those patients, tumours could no longer be detected at all.

The guest speakers at the American Society of Clinical Oncology Annual Meeting in Chicago included U.S. Vice President Joe Biden, who unveiled a public database for the gene sequences of cancer tumours. (Jim Young/Reuters)
At this point, avelumab hasn't yet been proven safe and effective. However, given the results of the clinical trial, pharmaceutical giant Pfizer plans to file for accelerated approval of the drug in the U.S.

Another much-discussed drug at the ASCO conference, pembrolizumab, seems to show even greater promise for Merkel patients, including Fred Ewart. 

study published in the New England Journal of Medicine in April reported that 14 of 25 patients had an objective response to the drug, and four of them had a complete response — nearly twice as high as the response to avelumab.

Patients in the avelumab study had already tried chemotherapy, which can suppress the immune system, while those in the pembrolizumab trial had not, which may explain why that drug produced a better response.

Merkel cell carcinoma usually first manifests in small, red, painless bumps like these. There are about 2,000 cases per year in the U.S. The skin cancer is associated with extensive sun exposure and fair skin, and found primarily in people over 50. (Paul Nghiem/Paul Nghiem Laboratory)

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.

When they work, both of these new immunotherapy drugs essentially take the brakes off of cancer-fighting T-cells: white blood cells that are part of the body's immune system and can sometimes be tricked into thinking that cancer 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 avelumab or pembrolizumab – except that there was no way to get him access to the drugs through the Canadian health care system.

Canada is one of the countries with "the most restricted access to publicly funded cancer drugs," compared to 12 other industrialized nations, a 2012 study found.

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

  • 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 submitted to Health Canada.
  • Once a new drug is approved, Canadians wait months longer for reimbursement compared to Americans, and patients in some provinces wait 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.

Preparations for cultivating cancer cells in a research laboratory at Oxford University. (Peter Nicholls/Reuters)

Rawson says Health Canada should explain why it takes such a long time to review new drugs. While it may be hampered by resource constraints, he says "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's family 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 cancer withdrawn in the U.S. and Canada in 2011.

2014 New England Journal of Medicine article found 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, more rigorous trials."

Life and death decisions

With neither avelumab nor pembrolizumab approved for Merkel cell carcinoma in Canada, and running out of time to get the drug on compassionate grounds — which his oncologist, Marcus Butler, was pursuing — Ewart decided to pay for pembrolizumab himself.

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

At first chemotherapy helped Fred Ewart, but his cancer soon returned. He's now on a new immunotherapy drug, pembrolizumab, which seems to be working. (Supplied by Ewart family)

Ewart had his first injection in late April, at the private Bayshore Clinic north of Toronto. The price 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 had improved and that he was in better 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. FDA–approved 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 found the average price of new cancer drugs in the U.S. was five to 10 times higher in 2012 than 15 years earlier.

Estimating that pharmaceutical companies have profit margins of 20 to 30 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 Merck will begin providing Fred with pembrolizumab (brand name Keytruda) for free, on compassionate grounds.