Terminal prostate cancer patients could get almost two more years of life with experimental immunotherapy drug, a study shows.
Men who had exhausted all other treatment options for end-stage prostate cancer trialled pembrolizumab.
Researchers described 1.6 per cent of the men as ‘super responders’ because their disease disappeared on scans after taking the experimental therapy.
They were surviving even after the clinical trial ended 22 months later, despite having a poor prognosis before treatment.
Overall, a quarter of participants showed evidence of the drug working, which could mean gaining extra time for those with little hope remaning.
Terminal prostate cancer patients could get almost two more years of life with experimental immunotherapy drug pembrolizumab (Keytruda)
According to the study published in the Journal of Clinical Oncology, the most dramatic responses were seen in patients whose tumours had mutations in genes involved in repairing DNA.
Researchers are now looking at whether this group might especially benefit from immunotherapy.
Pembrolizumab, marketed as Keytruda, is already used on the NHS for skin cancer, bladder cancer and lung cancer.
Immunotherapy works by helping the immune system recognise and attack cancer cells, the body’s natural way of fighting disease.
The typical treatment given to men with prostate cancer is hormone therapy, which reduces levels of the male hormones, called androgens, that lead to tumor growth.
Chemotherapy may also be given or radiotherapy for advanced or metastatic prostate cancer.
Johann de Bono, Regius Professor of cancer research at The Institute of Cancer Research, London, said: ‘We don’t see much activity from the immune system in prostate tumours, so many oncologists thought immunotherapy wouldn’t work for this cancer type.
‘But our study shows that a small proportion of men with end-stage cancer do respond, and crucially that some of these men do very well indeed.’
WHAT IS PROSTATE CANCER AND WHAT ARE THE SIGNS?
How many people does it kill?
Prostate cancer became a bigger killer than breast cancer for the first time, official statistics revealed last year.
More than 11,800 men a year – or one every 45 minutes – are now killed by the disease in Britain, compared with about 11,400 women dying of breast cancer.
It means prostate cancer is behind only lung and bowel in terms of how many people it kills in Britain. In the US, the disease kills 26,000 each year.
Despite this, it receives less than half the research funding of breast cancer – while treatments for the disease are trailing at least a decade behind.
- needing to urainte more frequently, often during the night
- needing to rush to the toilet
- difficulty in starting to urainate
- straining or taking a long time while urinating
- weak flow
- feeling that your bladder has not emptied fully
- blood in urine or blood in semen
‘Our study has shown that a small proportion of men with very advanced prostate cancer are super responders to immunotherapy and could live for at least two years and possibly considerably longer.’
Advanced prostate cancer is when cancer that originated in the prostate spreads to another part of the body, such as the bones or lungs.
In its early stages, prostate cancer is highly treatable, with five-year survival rates close to 100 per cent, according to The Cancer Research Institute.
Once prostate cancer has spread, however, the five-year survival rate falls to less than 30 per cent.
Scientists say there is a significant need for more effective treatment of advanced stage disease.
The study, led by The Institute of Cancer Research, London, and The Royal Marsden Foundation Trust, was a phase two clinical trial.
A total of 258 men with advanced prostate cancer were involved. They had previously been treated and became resistant to androgen deprivation therapy and docetaxel chemotherapy.
All patients received a 200mg dose of pembrolizumab every three weeks for up to 35 cycles.
One in twenty (five per cent) treated with the immunotherapy saw their tumours shrink or disappear, while 19 per cent showed some evidence of tumour response.
Among a group of 166 patients with particularly advanced disease and high levels of the protein prostate-specific antigen (PSA), the average length of survival was 8.1 months with pembrolizumab.
Nine of these patients saw their disease disappear or partly disappear on scans.
Of these, four were ‘super-responders’ who remained on treatment at the end of the study follow-up, with responses lasting for at least 22 months, scientists say.
A second group of patients whose PSA levels were lower, but whose disease had spread to the bone, lived for an average of 14.1 months.
PSA is a protien which leaks from the prostate. High levels signal a man may have prostate cancer and can be seen in blood tests.
Professor Paul Workman, chief executive of The Institute of Cancer Research, London, said: ‘Immunotherapy has had tremendous benefits for some cancer patients and it’s fantastic news that even in prostate cancer, where we don’t see much immune activity, a proportion of men are responding well to treatment.
‘A limitation with immunotherapy is that there’s no good test to pick out those who are most likely to respond.
‘It’s encouraging to see testing for DNA repair mutations may identify some patients who are more likely to respond, and I’m keen to see how the new, larger trial in this group of patients plays out.’
Leading charity Prostate Cancer UK said welcomed the findings but said larger studies were needed.
Dr Matthew Hobbs, deputy director of research, said: ‘Using the immune system to fight cancer has had incredible results in other cancers, however there are currently no immunotherapy drugs available to men with prostate cancer in the UK.
‘We are therefore pleased to see more evidence that this type of treatment could have long term benefits for some men with the disease.
‘Unfortunately, the number of men who do get positive results from the existing immunotherapy drugs remains very small.
‘We now need to find reliable ways to work out which men can benefit from these treatments, whilst also developing new immunotherapy approaches that work for more men. That’s why Prostate Cancer UK has recently announced up to £2million to fund research which will focus on these questions in 2020.’
Pembrolizumab was well tolerated, with 60 per cent of patients reporting any side effects. Only 15 per cent of patients experienced severe side-effects.
The study was funded by the drug’s manufacturer Merck, Sharpe & Dohme.
HOW DOES IMMUNOTHERAPY WORK?
Immunotherapy uses our immune system to fight cancer. It works by helping the immune system recognise and attack cancer cells.
Our immune system works to protect the body against infection, illness and disease. It can also protect us from the development of cancer.
The immune system includes the lymph glands, spleen and white blood cells. Normally, it can spot and destroy faulty cells in the body, stopping cancer developing. But a cancer might develop when:
- The immune system recognises cancer cells but it is not strong enough to kill the cancer cells
- The cancer cells produce signals that stop the immune system from attacking it
- The cancer cells hide or escape from the immune system
Immunotherapy is not yet as widely used as surgery, chemotherapy, and radiation therapy. Chemotherapy uses medication to kill cancer cells and radiotherapy means the use of radiation, usually X-rays, to treat illness.
Immunotherapy uses the natural power of your immune system to fight illnesses, and has been approved to treat people with many types of cancer.
There are different types of immunotherapy, some of which are also called targeted therapies or biological therapies.
Monoclonal antibodies (MABs)
Monoclonal antibodies are laboratory-produced molecules engineered to serve as substitute antibodies that can restore, enhance or mimic the immune system’s attack on cancer cells.
They are designed to bind to antigens that are generally more numerous on the surface of cancer cells than healthy cells. This process is called antibody dependent cell mediated cytotoxicity (ADCC).
Vaccines to treat cancer
Normally, vaccines help to protect us from disease, and researchers are looking at whether vaccines can be used as a treatment to help the immune system to recognise and attack cancer cells.
When you have the vaccine, it stimulates the immune system into action. The immune system makes antibodies that can recognise and attack the harmless versions of the disease.
Once the body has made these antibodies it can recognise the disease if you come into contact with it again. So you’re protected from it.
Cytokines are a group of proteins in the body that play an important part in boosting the immune system.
Interferon and interleukin are types of cytokines found in the body. Scientists have developed man made versions of these to treat some types of cancer.
Adoptive cell transfer
Adoptive cell transfer changes the genes in a person’s white blood cells (T cells) to help them recognise and kill cancer cells. Changing the T cell in this way is called genetically engineering the T cell.
This treatment is only available as part of a clinical trial in the UK. An example of a type of adoptive cell transfer is CAR T-cell therapy.
Source: Cancer Research UK