Why did cancer drug save one man while others died?

Researchers use Victoria man’s case to help find the answer

Why a cancer drug wiped out a late-stage aggressive cancer in former Victoria TV reporter Stephen Andrew while other metastatic patients on the same drug died, is a question researchers are racing to answer.

Dr. Christian Kollmannsberger, an oncologist at the B.C. Cancer Centre and clinical professor at the University of B.C., says just two years before Andrew was diagnosed, the development of new targeted drug therapies “took off like a rocket.”

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Targeted therapies and immunotherapy drugs flourished through clincial trials, and some can now be used in combination to give patients all possible options.

And yet doctors don’t know why some patients respond and others don’t.

“Whatever you want to call it, winning the lottery, lucky, God’s will, we don’t know at the moment what differentiates Stephen from other patients, but he definitely is an unusual patient,” said Kollmannsberger.

“Second opinions can save your life,” said Andrew, enjoying a coffee at a Victoria coffee shop. After his diagnosis, he went to Vancouver for a second opinion.

He had been diagnosed on Nov. 15, 2006, with Stage IV metastatic kidney cancer. He was 48.

Twelve days earlier — having run a half-marathon, exercised regularly and felt better than ever — he went to the bathroom before going on air. There was blood in his urine.

“Probably every second or third patient in my practice says I really didn’t feel much, said Kollmannsberger. “Their kidney cancer was detected because they were imaged for something else.”

It turned out Andrew had a 14-centimetre tumour. It had travelled to both his lungs, and would eventually reach and wrap around his spine.

About 6,600 kidney cancers were diagnosed in 2017 in Canada, and 1,870 died from the disease or about five people per day. Of those diagnosed nationally, 700 were in B.C. and 255 died. About 40 to 50 per cent of kidney cancers are attributable to smoking.

High-profile people who have died of the disease in the capital region in recent years include developer David Butterfield and former CTV reporter Jett Basi.

Each metastatic cancer patient is different in terms of how their cancer will progress, but based on averages, Andrew had about two years.

He was given few options, but used his position as a reporter to record his journey. It was a move that would benefit him personally, but also benefit an untold number of others when he pushed for the drug Sunitinib to be funded in B.C. at a cost of $7,500 a month in 2007.

Before the availability of these drugs starting in 2004, patients just had their kidney removed. Standard chemotherapy was largely ineffective.

When Kollmannsberger came to Vancouver in 2004, kidney cancer was considered one of most boring and hopeless tumours on Earth, he said.

“Nobody wanted to treat kidney cancer because there was nothing to treat,” said Kollmannsberger.

“Seventy-five per cent of our patients didn’t get any treatment at all — they were metastatic — apart from taking the kidney out,” he said. “The remaining 25 per cent got what we call today unspecific immunotherapy.”

Andrew was given few options. He went to Vancouver for a second opinion.

Kollmannsberger upped his dose of the targeted therapy Sunitinib, designed to slow or stop the growth of cancer tumours. Andrew missed the deadline for compassionate access to the drug, which had been part of a clinical trial with Canadian participation, and paid for it through his extended health care through work.

“I’m an enthusiastic clinical trialist — it offers my patients things they wouldn’t otherwise have,” said Kollmannsberger.

He argues that most drugs used in clinical trials are active and it’s just a matter of determining if they meet or exceed the standard.

After just six months, some of Andrew’s tumours had vanished, but a new lump appeared.

Old therapies would have given metastatic kidney cancer patients 12 to 15 months. But on Sunitinib there was hope.

“Stephen took this diagnosis and turned it around and formed it into almost a sense of being: I’ll take this and fight this and try to get as much positive out of this journey as possible, and that’s what he did,” said Kollmannsberger.

Andrew married his longtime partner, artist Danny Stewart, days after his diagnosis, and held a reception the next year.

For the past seven years Andrew has been disease-free, and for the past six years without any cancer-related drugs.

“He’s one of those one to two per cent who were cured by these modern therapies we have,” said Kollmannsberger.

“From a scientific point of view … a lot of groups in the world are working on why some patients are what we call exceptional responders, which Stephen absolutely falls into,” he said. “We don’t know what differentiates them, but they must have something that makes them uniquely sensitive to particular drugs.”

“The ideal would be if we can actually figure out why some patients respond fantastically to a drug A and why some patients don’t, and why some patients respond fantastically to a drug B and some patients don’t,” said Kollmannsberger.

Finding such bio-markers is going to change the way cancer is treated in the future, he said.

Such was the case when it was discovered that women who had HER2-positive breast cancer had a good chance to respond to the drug Trastuzumab.

“That knowledge would allow us to rationally apply our treatments to that patient for personalized medicine,” said Kollmannsberger. “Hopefully, one day in the not-so-distant future, we will be there.”

And while targeted therapies have come a long way — 10 to 11 drugs are approved for kidney cancer now, leading to considerably longer life spans — the future is immunotherapy, he said. “It’s a whole new chapter.”

New immunotherapies, which use the body’s immune system to fight cancer, are expected to replace Sunitinib as the first treatment for a large number of kidney-cancer patients, he said.

Of immunotherapy patients, 25 to 30 per cent have a remarkable benefit; 20 to 30 per cent a temporary benefit; and 30 to 35 no benefit.

Bristol-Myers Squibb Canada Co. this month announced approval of an immuno-oncology combination therapy of nivolumab plus intravenous injections of ipilimumab for treatment of adult patients with intermediate or poor-risk advanced or metastatic renal-cell carcinoma.

With Sunitinib, about one to two per cent would become disease-free, but with this new immunotherapy drug combination “we see it in 10 to 15 per cent — so it’s quite a big step forward,” said Kollmannsberger.

Better yet, it appears the two treatment groups — targeted agents and immunotherapies — don’t seem to have cross resistance, meaning they can be given one after the other.

“At the end of the day, God is on the side of the bigger battalions, so the more options you have, the higher the chance you’ll respond to something,” said Kollmannsberger.

Still, the question why some patients’ bodies respond and others don’t looms.

“We still unfortunately live in a time where in a number of patients the cancer just wins,” said Kollmannsberger.

“But what I think we can safely say is that if the cancer wins, it usually wins a lot later and the number of patients in which the cancer no longer wins is slowly but surely increasing.”

After leaving TV reporting, dabbling in communications and taking an unsuccessful run at being Victoria’s mayor, Andrew found his calling as executive director of Kidney Cancer Canada, whose mandate is to educate, support and advocate for kidney-cancer patients and their caregivers.

“He is relentless in a positive way by pushing for improving the situation for kidney-cancer patients, so that’s very admirable,” said Kollmannsberger.

Andrew advocates for patients to get a second opinion, try a clinical drug trial, get connected and find the care path that suits them.

“It saved my life,” said Andrew.

ceharnett@timescolonist.com

Kidney Cancer Canada fundraiser in September

In September, kidney-cancer patients, their supporters and advocates will be walking, running, riding or just simply moving in any way that fits their lifestyle and schedule to raise money for kidney cancer support and research.

This is the first year of Kidney Cancer Canada’s national fundraiser Move To Beat Cancer on Sept. 14-16.

The fundraiser encourages people to create a donor web page, collect sponsors, and then choose any time on that September weekend to move — walking, bowling, hiking, rowing, bicycling.

A group of riders will pedal from Montreal to Toronto and back committed to raise $20,000, while patient Paul Scott and his wife Marriane in Hespeler, Ont., will be walking trails.

Some patients will simply be walking the grounds around the hospital. Victoria’s Stephen Andrew and his partner, Danny Stewart, will be in Amsterdam that weekend, walking the canals.

Participants are encouraged to post pictures and videos to their personal pages to show examples of their activity. Bristol-Myers Squibb has pledged to match every dollar, up to $25,000, raised.

Andrew said the in-house fundraiser will put all the money donated into research and advocacy and education. Kidney Cancer Canada is a registered charity made up of patients, caregivers and health professionals who give support, education, advocacy for patients as well as funding for research.

To sponsor Andrew and others, go to: https://bit.ly/2M2i0tM

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