The closest thing yet to a cure for terminal cancer? | Science | The...

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The closest thing yet to a cure for

terminal cancer?
Immunotherapy has given Sandra Sayce an extra 10 years of life, and now new
combinations of the treatment may offer hope to many more patients
Sarah Boseley Health editor
Thursday 4 February 2016 10.21GMT

Sandra Sayce often nds she is seeing a new doctor when she goes for
her regular hospital check-ups. She has a suspicion they all want to
meet her. The NHS doesnt do miracle cures and nobody, including
Sayce, is prepared to say that her advanced skin cancer has been
beaten. Yet the last treatment she had for stage 4 melanoma, which
normally kills within months, was nearly 10 years ago.
Sayce is one of the longest survivors of a new approach to cancer
treatment that has had cautious and weary doctors almost punching
the air in excitement. The 52-year-old is alive and well thanks to the
groundbreaking work of the Royal Marsden in London, the worldleading cancer hospital. Its patients and those referred from other NHS
hospitals, as Sayce was, are invited to take part in clinical trials. It is at
the cutting edge of cancer drug discovery.
Western countries have been steadily ghting back against cancer in
recent decades: Britain has recorded a 10% decline in death rates over
the past 10 years.
But growing numbers of people are still being diagnosed with the
illness. Traditional chemotherapy kills healthy cells as well as cancer
cells and there is always the possibility the disease will come back.
For Sayce, initial treatment in 2001 had appeared to clear three lesions
found in the lower part of her right leg, but in 2005 they returned with
a vengeance. She was then given immunotherapy, which teaches the
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bodys defensive immune system to identify cancer cells and attack

them from within, in the same way it would ght o a cold.
After the treatment, the cancer disappeared. It took me a couple of
years to believe it was true, she said at her home in Ruislip, west
London. You never quite lose that concern at the back of your mind,
but there is no active disease and I have been stable for so long, she
added. My consultant said to all intents and purposes there is no
reason why it would come back, but we are in territory where we dont
really know.
Sayce knows how lucky she has been. A GP spotted her cancer during a
consultation for a damaged knee. She said whats that lump on the
front of your shin? recalled Sayce, who had thought nothing of it. A
biopsy revealed melanoma a form of skin cancer.
She would never have expected it. I have never been on a sunbed. Ive
been on one sunny summer holiday as an adult. But I grew up in the
late 60s and 70s and we got shoved out in the garden and burnt to a
crisp, then covered in calamine, she said. I get really cross when I see
children unprotected today.
She had surgery to remove not one lump but three, and when one of
her lymph nodes was found to be positive for cancer, the whole lot
were taken out. She had intensive chemotherapy to the leg.
Then it was all quiet until the summer of 2005, she said. I was on
holiday in Norfolk. On the Wednesday, we won the bid for the London
Olympics and I was so excited because I love sport and it was coming
to my home town. The next day was 7/7 so I was checking my friends
were OK. It was during that week I started to notice little black spots
appearing on my leg. You could almost sit and watch them appear. It
was quite scary.
She phoned St Thomas hospital in London, where she had been
treated, and got an appointment within a couple of days. A biopsy and
a PET scan showed cancer in the leg, liver and the lymphatic system.
This was advanced melanoma, classied as stage 4, which has a very
poor prognosis. She was given six months of the standard
chemotherapy treatment, decarbazine, which slowed it down but the
tumours continued to grow. It bought me some time, she said. It is
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very cheap and it was all they had then.

The only other option was to join a trial at the Royal Marsdens Sutton
site in Surrey. For 12 weeks from May to August 2006, she spent every
Friday in the Oak ward with six men who had prostate cancer and one
who, like her, had melanoma. The trial drug, known only as 17AAG,
stank, she said. It absolutely reeked. It smelled of sweetcorn. And it
did her no good. On 29 September 2006, she started on a second trial,
of a drug called ipilimumab. It was a novel approach, designed, she
was told, to reprogramme her immune system.
She had just four treatments one a month from September to
December. I had a head-to-toe rash, which itched, she said. But I
knew quite quickly that it was doing something. The lesions in her
leg, which had become lumpy, started to atten.
She still has shadows on her legs, but no active cancer any more. The
lesions in her liver and spleen disappeared. She has had no further
treatment and there is no sign of cancer.
The word cure is tricky obviously and thats quite important, said
her consultant, James Larkin, at the Marsden. To say someone is
cured of a metastatic cancer means they then need to have a normal
life expectancy and die of another cause 10, 20, 30 years later. So, of
course, we hope that its going to result in cures but actually you cant
really say that because its too early. But lets say that early indications
are promising.
Cancer can evolve to be able to survive the toxic drugs thrown at it,
just as bacteria become resistant to antibiotics, said Larkin. The
critical dierence with immunotherapy is that you are actually
reprogramming the immune system, if you like. The idea is, if the
tumour does change and evolve, the immune system can also change
and evolve with the tumour. I cant exactly prove that but I
fundamentally think thats the critical dierence.
The drugs, he thinks, can teach the immune system to watch out for
cancer returning in a slightly altered form, which in the past would
have slipped below the bodys radar. Its easy to make these kind of
statements, he said almost apologetically. But I think the clinical
experience with a drug like ipi, which weve been using for almost 10
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years now, does bear that out.

Larkin is hugely enthusiastic about the research being done and the
potential for patients. He persuaded a leading US pharmaceutical
company to open an arm of a trial using ipi as everybody now calls it
and a newer immunotherapy drug, pembrolizumab, at the Marsden
as well as the world-famous US hospitals. He succeeded in enrolling
more people on to the trial than any other centre. Alone, the drugs can
have great results with several types of cancer kidney, bladder, head
and neck as well as melanoma but in only 20-25% of patients. The
hope was that a combination might help more.
At the big annual cancer drug conference last May, in Chicago, the
results had everybody reaching for superlatives. Nearly 60% of the
patients with advanced melanoma on the trial given the combination
were stabilised or their tumours actually shrank by the end of a year.
Although there were side eects not seen when one of the drugs alone
was given, immunotherapy worked for most of the patients, not just a
small proportion of lucky people such as Sayce.
It was the moment when immunotherapy began to look like a
mainstream treatment. Larkin and his fellow researchers cant yet
know how long the eects will last or how good survival rates will be,
but the mood is optimistic. Im 43, he said. I certainly hope that
within my working lifetime well be in a position where the majority of
people dont die from this disease.
Prof Martin Gore, medical director at the Marsden, who is also a
melanoma and kidney cancer specialist so has shared in the
excitement over immunotherapy, believes research should be integral
to cancer care. It is a core philosophy at the Marsden; Gore thinks it
should be NHS-wide. Trials give patients a chance of better, more
eective treatment for themselves and for others to come.
People say it is all right for the academics but we cant do that. Were
too busy, he said. Id quite like to see that being challenged a bit,
saying, come on. I do it why dont you do it? If you are a doctor, by
denition you should be interested in research. Our colleagues at the
GMC [the General Medical Council, which regulates doctors] expect us
to keep up to date.

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It is not that people dont want to do it. It is that people are too busy.
Many peoples jobs are incredibly crowded with clinical work. In some
places, the oncologists are very embattled with the number of patients.
That goes for general practice in spades. I think we need to look at that
a bit to know how we can change the way we work so we have
breathing space. I think we have a way to go in terms of challenging the
system to allow people to do it or even expect people to do it.

Topics
Cancer (Science) Cancer (Society) Health Medical research Doctors
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