Emerging Therapies and Treatment Options

Because every cancer profile is different, each cancer needs a custom treatment.

Worldwide, there are many emerging therapies being tested on patients in clinical trials. There are some already showing highly promising results in those trials for the treatment of prostate cancer.

Precision Medicine

Scientists are working on ways of matching specific treatments to the particular genetic make-up of the patient and the tumour. Cancer cells are mutations and each mutation is unique with its own weaknesses. Analysing the cancer and then having a custom-tailored treatment to attack those specific weaknesses has been shown to have the potential to be effective. But the scientists themselves say there is a long way to go.

PARP Inhibitors

PARP is an enzyme that helps repair DNA when it becomes damaged. A PARP inhibitor blocks the enzyme and keeps cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors, which include olaparib (Lynparza®), rucaparib (Rubraca®), niraparib (Zejula™), and others, are a class of precision medicine treatments that are effective against cancers with mutations in genes that repair damaged DNA. These ‘DNA damage repair’ (DDR) genes include the breast and ovarian cancer risk genes BRCA1 and BRCA2. Approximately one-third of metastatic prostate cancer patients have these mutations in their tumours and may be candidates for treatment with PARP inhibitors. These drugs need further studies and trials, before being approved by NICE for use in ths country, but it is hoped that in the future, screening of metastatic prostate cancer patients to identify those who have gene mutations and may benefit from PARP inhibitors will become common practice.

The Immune System

Our immune system works by protecting the body and is trained to fight infection, illness and disease; it can also protect us from cancer developing. It is doing this continually and is daily killing cancer cells without us realising it, by means of its killer T-cells. T-cells have proteins on them that turn on an immune response and other proteins that turn it off. These are called checkpoints. The immune system includes the lymph glands, spleen and white blood cells. Normally it can detect and destroy faulty cells in the body, stopping cancer developing. However, tumours have a few tricks they can play on our immune system such as:

  • The cancer cells produce signals that stop the immune system from attacking it
  • The cancer cells hide or escape from the immune system
  • The immune system recognises cancer cells but is too weak to kill them

What is Immunotherapy?

Immunotherapy has become a standard treatment for some types of advanced cancer, both lung and skin cancers have been treated with immunotherapy drugs. It is now being developed for advanced prostate cancer patients. It works by helping the immune system to recognise and attack cancer cells and can be delivered on its own or with other prostate treatments such as chemotherapy or radiotherapy. Some treatment types of immunotherapy are also called targeted treatments or biological therapies.

Some men with otherwise untreatable prostate cancer can benefit from an immune system-stimulating treatment which could help prolong their life, or even stop their cancer growth entirely. Previous trials using immunotherapy in prostate cancer have been unsuccessful, but the latest research examined the genetics of the tumours.

A UK trial of 258 men using a drug called pembrolizumab, found that immunotherapy can benefit some patients with advanced prostate cancer, most likely those patients who have specific DNA repair mutations within their tumours. When treated they lived much longer. As the therapy will not work for all patients, the next stage is to predict who would best respond to the treatment.

Still at a very early stage, an emerging treatment is CAR-T cell therapy which involves taking out a person’s own immune T-cells, altering their DNA to spot cancer cells, and then putting them back into the patient to seek out and destroy tumours.

Immune Checkpoint Inhibitors

Immune checkpoint inhibitors are a class of immunotherapy that activate tumour-killing immune cells. Pembrolizumab (Keytruda®) is one of a range of drugs called ‘checkpoint inhibitors’ being developed by pharmaceutical companies; they are also described as a Monoclonal Antibody (MABs) or targeted treatment. Antibodies are found naturally in our blood and help us fight infection. MAB therapies mimic natural antibodies, but are made in the laboratory. MABs trigger the immune system by attaching themselves to proteins on cancer cells, making it easier for our own cells to find and attack the cancer cells. By stopping the cancer turning off the immune system, the body can keep on attacking the tumour.

Many studies are underway in prostate cancer to test other checkpoint inhibitors, including pembrolizumab, ipilimumab (Yervoy®), nivolumab (Opdivo®), durvalumab (Imfinzi™), atezolizumab (Tecentriq®), and avelumab (Bavencio®) alone and in combination with various therapies including PARP-inhibitors, cancer vaccines, and radiation therapy.

Vaccines

Researchers are also testing vaccines to treat cancer. Normally vaccines help protect us from disease and are made from weakened or harmless versions of the disease they are intended to fight. A vaccine can stimulate the immune system into action, by recognising and attacking the harmless versions of the disease. Once the body has made these attacking antibodies, it can recognise the harmful versions of the disease and mount an attack against those cells. Researchers are developing vaccines to recognise proteins that are on particular cancer cells, which helps the immune system to recognise and mount an attack against those particular cancer cells.

Genetic Testing and Counselling

It has been known for a while that around 5% of men with prostate cancer inherit from their parents mutations in the genes responsible for repairing damaged DNA (which include BRCA1 and BRCA2 but there are many more). Newer research suggests the percentage increases to over 11% in men with advanced prostate cancer. Men with these mutations are more likely to do better on certain types of treatment.

These results suggest that, in the future, men with advanced prostate cancer should be tested for DNA damage repair mutations as it could improve their chances of getting the right treatment. In those cases where such a mutation is found the man’s family may then be offered genetic counselling and testing for the DNA damage repair mutations.

Proton Beam Therapy

For men with early-stage, localised prostate cancer, conventional radiotherapy uses photons that produce high-energy radiation beams that destroy the cancer cells, but to get to them the beams must pass through healthy tissue and the beams also carry on beyond the tumour site, this can cause damage to other organs, particularly the rectum, and create side effects.

The potential advantage of protons over photons is that there may be significantly less collateral damage. The proton beam can be very accurately focused such that the major part of the energy is targeted at the cancer to be treated. Damage to tissues surrounding the cancer is significantly reduced. It should be noted that this type of therapy is only suitable for around 15% of all cancers.

Currently the therapy is employed for eye and some brain cancers, but a small number of patients have been treated for prostate cancer with promising results. By 2020 the UK should have 4 Proton Beam Centres: two NHS units in Christie Hospital Manchester and University College Hospital, London; two privately funded units at the Rutherford Cancer Centres in South Wales and Reading.

Proton beam therapy is yet to be widely used in the UK, but considerable experience has been gained in other countries. Long-term outcomes are promising and increasing data will become available.

Stereotactic Ablative Radiotherapy (SABR)

CyberKnife® is one of several types of radiotherapy machine that can deliver SABR. This form of radiotherapy uses pencil-like beams of radiation that are directed from different angles precisely onto the tumour. The X-rays are contained in a robotic arm, giving the advantage of being able to direct the beams to any part of the patient with greater accuracy, higher intensity and avoiding, to a large part, collateral damage to nearby healthy tissue. The scanner moves with exceptional agility and is able to track any slight movement of the patient or his prostate.

Stereotactic treatment can treat complex tumours wrapped around sensitive structures. It is used for a number of cancers where precise targeting is essential, and it is undergoing a trial for certain prostate cancers that would benefit from this treatment. Fewer treatment sessions, using a higher dose than conventional radiotherapy, are generally needed. However, it has not yet been proven whether this method is any safer or better than IMRT or IGRT.

There are currently only a few NHS hospitals and private clinics in the UK that have CyberKnife®. These include the Royal Marsden Hospital, St Bartholomew’s Hospital and some London clinics.

Diagram of CyberKnife®

Cameras (3 sets) for synchrony systems          X-ray source  

  
Linear accelerator treatment head with collimator        Robotic delivery system