In 2004, Trevor Sauer noticed that a birthmark on his shoulder had begun to grow. Doctors diagnosed him with melanoma, a potentially deadly skin cancer, and the lump was removed. But in 2006, just two months into his marriage, a routine CT scan showed spots on his liver and kidney. His melanoma had spread and doctors told him he had six months to a year to live.
FUTURE PLANS: Trevor Sauer fights the odds against melanoma and enjoys cancer-free life with his family.
Photos By Christy Dean
Sauer spent a year on dacarbazine, the traditional chemotherapy treatment, but his cancer continued to grow.
“This is a cancer that often hits people at a younger age, with young families, and at the beginning of their careers,” Dr. Michael Smylie says. “And, up until five years ago, we had absolutely no effective treatment.” Smylie treats melanoma patients at Edmonton’s Cross Cancer Institute. For a long time, the only approved treatment for the disease was a mid-1970s-era drug of questionable efficacy called dacarbazine. Even the Food and Drug Administration of Canada questioned if it worked any better than a placebo. “Melanoma was a very depressing tumour to treat,” Smylie says. “For a long time we didn’t understand the biology.”
Then, in 2005, a clinical trial opened for a new immunotherapy drug called ipilimumab that Smylie was skeptical about it at first. Thirty other clinical trials he had conducted since 1994 had all failed to improve survival rates.
The following year Smylie’s patient, Trevor Sauer, found out he was eligible to take part in an early trial of ipilimumab for patients with stage four melanoma. The paperwork was intimidating – stacks of possible side-effects and waivers – and the nausea and diarrhea almost hospitalized him.
“But I didn’t have any second thoughts about the clinical trials. I had end-stage melanoma: what did I have to lose?” he says. “We thought, ‘I can try it and, if it gives me another year or three months, it’s better than the alternative.”
Due to Sauer’s and other patients’ response to ipilimumab, Smylie’s opinion of the drug changed. Smylie saw early on that this drug was different because many patients in the trials had dramatic responses to it and their cancer went away. The ipilimumab trial closed in 2008 and he expected to see the survival data back a year later, as per usual, because the unfortunate reality was that most of his previous clinical trial patients died within a year. It took more than three years to get the survival data back for this trial. “That was the first clue that this drug was really working,” he says.
Ipilimumab is an immunotherapy drug that is part of a much larger, new approach to cancer treatment. Immunotherapy offers to treat cancers and patients in a more targeted way based on immune differences and genetic mutations that are particular to the patient. The success of ipilimumab inspired the New England Journal of Medicine to dub melanoma the “unlikely poster child of personalized cancer therapy.” Cancer cells play incredibly wily tricks on the body’s immune system to avoid attack. Over a hundred years ago, a young New York surgeon named William Coley had a theory that the immune system could be used against cancer. He’d seen one patient make a complete recovery after getting an infection that forced his immune system into overdrive. The patient beat the infection, and his cancer disappeared with it.
Coley had a difficult time collecting the data to prove his point. Radiation therapy had much more than anecdotal evidence supporting its effectiveness in treating cancer, and it eventually became the treatment of choice. Chemotherapy and radiation predominated cancer treatment throughout the 20th century.
Smylie first took on melanoma because it was the file every “new guy” got – no one wanted do it. No one, it turned out, except him. He stayed with the disease because of the phenomenal patients he worked with and because he was drawn to clinical research. And since there was still no effective treatment when he was the “new guy,” the best treatment for melanoma was clinical research trials.
“Ipilimumab is only the first step. Another European researcher said that we know we are being successful because in the past 15 years, none of the really bright graduate students wanted to study melanoma,” Smylie says. “Now, some really bright people are saying, ‘I want to do melanoma research as a career.’ ”
It’s only in the last five years that researchers have even begun to understand the immune system well enough to begin to manipulate it.
“Since 1972, when Nixon declared war on cancer, we had made very little impact in the following 30 years,” says Smylie. “However, in the last seven years, we’ve been able to transcribe growing knowledge of cancer and immune systems to effective treatment.”
Ipilimumab – Yervoy is its trade name – works to stimulate the large white blood cells called T-cells, which fight foreign microbes in the body. In the 1980s, researchers noticed that in the presence of cancer, T-cells weren’t receiving the usual signals to attack a foreign invader. Researchers eventually discovered what was holding the T-cells back: a protein called CTLA-4.
By injecting an antibody into CTLA-4 (ipilimumab), the T-cells are effectively given a green light to attack the invading cancer cells. Smylie explains, “Ipilimumab is giving the body a tool; it is not treating the cancer, but treating the immune system. We are trying to get the immune system to attack the cancer.”
While treatment options are slowly changing, there is a great deal more to understand: Why do some people respond completely to ipilimumab and others not at all? What role do individual gene mutations have in cancer cells that are flourishing? What other cancers will respond to ipilimumab or to immunotherapy?
French designer Coco Chanel donned a very public and accidental tan in 1923 as she stepped off her yacht to a swarm of reporters waiting for her on the dock in Cannes. She claimed her bronze skin was intentional and will be a new trend. And it was. Fast-forward 70 years and tans are still the trend. Melanoma rates have exploded and are expected to affect one in 75 Canadians by 2015, up from one in 1,500 in 1935.
“Melanoma is a completely preventable disease, in most cases,” Smylie says. One of his patients, a 25-year-old woman with months to live, went back to the tanning company she’d frequented for years. She told the owner about her terminal cancer and he shrugged and said, “Just cut it off.”
For many patients with melanoma, surgery will effectively remove the cancer cells. However, if the cancer manages to spread, the diagnosis is dim. Just five years ago,
the average life expectancy for most patients with metastatic melanoma was six to seven months; 75 per cent of patients died in the first year, and 90 per cent by the second year.
After previous years of no effective treatment, the ipilimumab clinical trials showed a marked improvement in survivor rates: from about five per cent to 20 per cent. The results led Health Canada to approve the use of ipilimumab in 2012 for treatment of metastatic melanoma in patients who had not responded to first line treatments.
Now, 20 per cent of patients are living for five years or longer. “I’ve treated melanoma for almost 20 years, and it’s been 17 years of depression and three years of euphoria,” Smylie says. He now has 10 patients who are cancer-free. Trevor Sauer is one of them.
Years of patience and hard work (by researchers), and trust and risk (by patients), have led to melanoma treatments that transform lives. Sauer went from facing a death sentence, to enjoying a full life, cancer-free. Not only is he alive seven years after being diagnosed with metastatic melanoma; he has been cancer-free for five years. He continues to defy the odds: despite exposure to radiation and chemicals that leave most people infertile, Sauer and his wife conceived a baby girl. At three years old, Sophia is happy, healthy, and a reminder that clinical research trials can lead, literally, to new life.
Under Your Skin
SMOKE THAT: The World Health Organization has named UV rays as a class-1 carcinogen: the same as tobacco smoke.
GROW UP: Alberta remains one of the only provinces (along with Saskatchewan) to allow minors to use tanning beds without parental consent.
TAKE THE 5-S CHALLENGE: One in 25 Australians will be diagnosed with melanoma. A public education campaign, “Slip, slop and slap” is geared towards reversing this trend. In other words, slip on a shirt, slop on sunscreen, and slap on a hat. They recently added “seek” (shade) and “slide” (on sunglasses).
LISTEN, LADIES: Melanoma is a leading cause of cancer-related death in women aged 25 to 35.