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Historic cancer trial sees Swansea at the forefront of a medical revolution

Professor Wagstaff opened the new clinical trials suite earlier this year

A global trial in which Swansea was a leading player has been a game-changer in the treatment of a particularly aggressive type of cancer.

Analysis of a clinical trial that used a combination of drugs to treat metastatic melanoma, or skin cancer which had spread around the body, shows that almost half of patients are surviving 10 years or more.

This compares with 2011 when the average survival was just six-and-a-half months.

The Cancer Institute at Singleton Hospital was one of the sites around the world that participated in the trial, called CheckMate 067, in 2013-14.

It involved using two immunotherapy drugs instead of chemotherapy, with remarkable results.

For medical oncologist Professor John Wagstaff, who has now retired from the Cancer Institute, the results mean he has ended his career on a high.

Professor John Wagstaff with Maria Johnstone, the only research in the Cancer Institute to have been involved with the trial from start to finish

“Going back 10-15 years we used chemotherapy to treat metastatic melanoma and that was really not a very good treatment at all,” he said.

“Only about one in five people would get shrinkage of the melanoma. The average survival was around eight or nine months and virtually no-one survived longer than two years. It was a pretty dismal disease to have.

“We’ve known for 30 years that the immune system does try to keep the melanoma under control. It’s just not very good at doing that on its own.

“The drug companies started to develop new medicines that work by boosting the body’s immune system.

“There were basically two main drugs that were developed. One was a drug called Ipilimumab, which was tested in clinical trials.

“Analysis was undertaken of all the clinical trials that had been done, which had just a little bit shy of 5,000 patients worldwide.

“That showed that that drug on its own would get control of the melanoma at 10 years in about 20 per cent of patients.

“That was really the first time that it been shown that a drug that works through the immune system could actually get long-term survival benefits for patients.”

The next drug to be developed was called Nivolumab. At that time, 10 years ago, there were no long-term results from that drug on its own.

The 067-trial split the patients into three groups. One received Ipilimumab, which was standard treatment at that time. A second group got Nivolumab on its own and a third group got the two drugs together.

“There were just shy of 1,000 patients in that trial, worldwide,” said Professor Wagstaff.

“There were five centres in the UK that took part in it. We recruited 17 patients from across Wales, and one from England. We were the fifth or sixth highest recruiting centre in the world and I’m co-author of all the publications that have been published about the trial.

“It was a trial that recruited extremely quickly worldwide, and the results were quite spectacular. With the combination treatment, the shrinkage rates were up at around 65 per cent.

“And then, as time went by, it became clear that the remissions we were seeing with these treatments were much better than what we were seeing previously.”

Five years after the trial, analysis showed that 53 per cent of the patients who received the combination of drugs were still alive. With Ipilimumab alone it was at around 23 per cent.

Earlier this year, the 10-year analysis showed that 43 per cent of patients with the combined treatment were still alive.

“One of the other most important things about this trial is that we looked at all the patients who were in remission three years after they started treatment and looked what happened to them at 10 years,” said Professor Wagstaff.

“And only three per cent of the patients who were in remission at three years died of melanoma by 10 years. So virtually nobody has had a recurrence of their melanoma from between three years and 10 years.

“This suggests that these people are actually cured of their metastatic melanoma.  So, we’ve gone from a situation where you had a pretty uniformly fatal cancer to one where we’re curing a little bit less than half of the patients.”

The report into the 10-year outcomes has been presented at a major European cancer conference in Barcelona and the results published in the New England Journal of Medicine.

Professor Wagstaff described it as fantastic news for patients, which had changed the treatment of melanoma worldwide.

“It’s a little bit like patients with testicular cancer in the 1980s or 1990s, when we first started treating those patients with platinum-based chemotherapy,” he said.

“Testicular cancer used to be, again, a disease that people died of very, very quickly once they were diagnosed with metastatic disease. With platinum-based chemotherapy, you’re curing 80 per cent of the patients. It’s that kind of sea-change we’re seeing with this treatment.

“The interesting thing is, melanoma was the first cancer that these treatments were tried in but subsequently there have been clinical trials in non-small cell lung cancer, in kidney cancer, quite a wide range of cancers, and this treatment is effective in a broad variety of other cancers as well.

“We took part in a trial with metastatic kidney cancer using the same treatment. It doesn’t work quite as well in kidney cancer but you’re getting long-term survival in around about a third of the patients.”

The Cancer Institute was built following a £1 million charity appeal run in conjunction with the South Wales Evening Post, leading up to the opening of the South West Wales Cancer Centre in 2004.

The SWWCC provides the infrastructure for the Institute’s research delivery team, together with cancer and haematology clinicians, to run various UK and global trials.

Earlier this year, the Institute moved to its purpose-built new home, a dedicated clinical trials suite alongside the Chemotherapy Day Unit on Ward 9 at Singleton Hospital.

Funding from the Welsh Government, first via the Wales Cancer Research Network and now by Health and Care Research Wales, has supported the growth of cancer research within the health board.

There can be 30 trials running at any one time. Many have led to huge strides in cancer treatments, with Swansea’s success in recruiting patients making it one of the UK’s leading sites.

Professor Wagstaff arrived in Swansea in 2003 as part of the development of Swansea Medical School.

“When I first came here, there were almost no clinical trials going on at all,” he recalled. “Now we’re regarded, certainly in melanoma and kidney cancer, as one of the top centres in the UK and also recognised internationally.”

Dr Nicola Williams, National Head of Support and Delivery at Health and Care Research Wales, added: “This groundbreaking trial demonstrates the power of research to transform survival rates for this type of cancer, giving hope to patients across the world.

“Singleton Hospital has become one of the UK’s leading cancer research sites, with the capacity to have as many as 30 trials running at any one time and a hugely successful track record for recruiting patients.

“Health and Care Research Wales is very proud to have supported the growth of cancer research within the health board.”

The South West Wales Cancer Centre is run by Swansea Bay University Health Board and provides a range of lifesaving NHS treatments such as radiotherapy, chemotherapy, and immunotherapy.

It celebrates its 20th anniversary this year and a fundraising appeal has been launched by Swansea Bay Health Charity, the health board’s official charity, to commemorate the landmark.

The appeal, Going the Extra Mile for Cancer, will support the thousands of patients from the Swansea Bay and Hywel Dda areas who are cared for there every year, as well as relatives and staff.

To support the Going the Extra Mile for Cancer appeal, click on this link:

https://swanseabayhealthcharity.enthuse.com/cf/going-the-extra-mile-for-cancer