Half of people diagnosed with advanced melanoma, which once had dismal survival rates, are now living for five years or more when they receive a combination immunotherapy treatment, a study has shown.
A decade ago, only one in 20 patients were still alive after five years. Most died within six to nine months. Researchers from the Institute of Cancer Research and the Royal Marsden hospital in London, who have pioneered the work, said the five-year survival rate for just over half of their patients was a landmark.
While they could not talk of a cure, they said they hoped some people would go on to have a normal life expectancy.
Immunotherapy, which teaches the immune system to fight the cancer and is an alternative to bombing tumours with drugs, has had remarkable results. Ipilimumab and nivolumab, two monoclonal antibodies, have both helped prolong lives and the new study showed that, in combination, the results were even better.
“By giving these drugs together you are effectively taking two brakes off the immune system rather than one so that the immune system is able to recognise tumours it wasn’t previously recognising and react to that and destroy them,” said Prof James Larkin of the ICR who presented the results at the European Society for Medical Oncology meeting in Barcelona.
In their paper published in the New England Journal of Medicine, the team explain that they recruited 945 patients with advanced melanoma and randomly assigned them to one of three groups: 314 patients received the “double-hit” of nivolumab plus ipilimumab; 316 patients received nivolumab plus a placebo; and 315 patients received ipilimumab plus a placebo. Each nivolumab arm was compared with ipilimumab by itself, and was administered until the disease progressed or until any side effects became unacceptable.
The best results were seen in the group who had the combination treatment, 52% of whom survived to five years or more. Most of those, 74%, were no longer receiving any treatment by that time. The overall survival for nivolumab alone was 44%, and 26% for ipilimumab.
Larkin said there had been little change in their patients between three and five years and they were hopeful they would continue to do well.
“The chance of being alive at five years is quite similar to three years and four years,” he said. “For those patients getting to five years, many or most are off treatment and leading normal lives.”
At the Royal Marsden, Larkin said he had now treated about 100 patients with advanced melanoma or advanced kidney cancer with the combination, which has been approved for use in the NHS for both conditions.
The drugs have only been available for 10 to 15 years so the long-term outlook cannot be certain until people have survived into old age. “The definition of a cure is to have a normal life expectancy and die of something else,” he said.
Some people cannot tolerate the side effects of immunotherapy drugs and have to stop them within weeks of starting. But the researchers found that did not matter; even taking immunotherapy for a limited period appeared to kick-start the immune system into recognising and fighting the tumours. The survival rates among those who stopped were as good as in those who continued.
For advanced melanoma, the standard course of treatment is two years, but some people may need much less, Larkin said.
Pamela Smith, 67, joined the immunotherapy trial in January 2014, soon after discovering her melanoma had spread.
“It was inoperable, so the trial was my only option,” she said. “I’d been having treatment every two weeks for about four months when I developed diarrhoea that was so bad I had to come off treatment. Amazingly, the first scan and every scan since has shown that in that relatively short time it worked. My tumour shrank to less than half its original size and it hasn’t changed in five years.
“I’ve not had any treatment since and I feel brilliant. At every appointment at the Royal Marsden, they ask how I feel on a scale of one to 100 and I answer 100. I feel well and very lucky to be alive.”
