Hello, everyone
This month in our Health in Focus series, we’re looking at targeted therapies. Cancer cells behave differently from healthy cells in a number of ways. These behaviours can make them more vulnerable to damage. Targeted therapies are drugs that disrupt this abnormal behaviour, causing the cells to die.
Targeted therapies are usually given in addition to surgery and chemotherapy for ovarian cancer, as maintenance therapies. Their role is to reduce the risk of the cancer recurring and to prolong the time between treatments if it does. This can give people longer periods of feeling well before they next need treatment.
Because targeted therapies are less likely to affect healthy cells, many people find that their side effects are more tolerable than chemotherapy and become easier to manage over time. As with any drug, some people will find them easier to tolerate than others. If you’re experiencing side effects that are difficult to cope with, your team may be able to reduce the dose, which can make them more manageable
Our information booklet about targeted therapies is available at:
ovacome.org.uk/targeted-the...
In this second post in our series on targeted therapies, we will be focusing on PARP inhibitors, which are drugs that target cancer cells by preventing them from repairing damage to their DNA. We’ll look first at their availability, how they’re given and their side effects and then we’ll outline how they work.
At the moment, there are three PARP inhibitors available to treat platinum-sensitive stage III-IV high grade serous ovarian cancer. Their availability is different depending on where in the UK you live, so we’ve summarised it below:
Olaparib (‘Lynparza’)
•First and second line through the Cancer Drugs Fund in England and its Welsh and Northern Irish equivalents for BRCA-positive people who meet the criteria.
•Routinely available third line through the NHS in Scotland for BRCA-positive people who meet the criteria.First line via the NHS Scotland Patient Access Scheme for BRCA-positive people who meet the criteria.
Niraparib (‘Zejula’)
Second-line or later via the Cancer Drugs Fund in England and its Welsh and Northern Irish equivalents for people with and without BRCA mutations who meet the criteria.
Second line in Scotland for people without BRCA mutations who meet the criteria.
Rucaparib (‘Rubraca’)
Second-line or later via the Cancer Drugs Fund in England and its Welsh and Northern Irish equivalents for people with and without BRCA mutations who meet the criteria.
Second line or later in Scotland for people without BRCA mutations who meet the criteria.
There have been a number of changes to the availability of PARP inhibitors recently, and there are ongoing appraisals which are likely to result in further changes. We recommend asking your team for advice on current availability.
Unlike Avastin (which we covered in last week’s post at:
healthunlocked.com/ovacome/..., PARP inhibitors are tablets, so you can take them at home and don’t need to go to hospital for your treatment. They must be started within eight weeks of the last dose of chemotherapy, according to the current availability criteria, so if you want to explore whether they’re an option for you it’s important to do so as early as possible.
As all three drugs work in a similar way, their side effects are similar too, although there are some differences between them. If PARP inhibitors are an option for you, your team will advise you on which would be suitable. Some common side effects of PARP inhibitors include:
•Digestive side effects, including nausea, diarrhoea, constipation, indigestion/abdominal pain, taste changes and loss of appetite;
•Effects on the blood cells, including low red cells (anaemia) leading to tiredness and breathlessness, low white cells leading to increased risk of infection and low platelets, leading to bleeding and bruising;
•Tiredness;
•Headaches, dizziness and sleep disturbances;
•Mouth ulcers.
This isn’t a complete list of potential side effects, and you can find more information about the side effects of each individual drug in the links at the end of this post.
The DNA in our cells can become damaged in a number of ways, for example when it’s copied before a cell divides into two new cells and occasional copying errors are made. For this reason, our body regularly checks our DNA for damage and repairs it.
There are a lot of different proteins involved in DNA repair, including ‘PARP.’ PARP sticks to a damaged area and attracts other proteins to repair it. The aim of inhibiting PARP is to make cells less able to repair damaged DNA so that more damage accumulates and the cell dies.
Cancer cells divide more rapidly than other cells and they are doing so in abnormal and uncontrolled ways. This makes them more vulnerable to DNA damage, and therefore a target for PARP inhibitors.
You may have heard or read about a connection between the effectiveness of PARP inhibitors and BRCA or other genetic mutations. As we mentioned above, there are numerous other proteins that help to repair DNA, so even if PARP is blocked by an inhibitor these other proteins can still work.
Some people have genetic mutations which mean that one or more of these proteins is missing or doesn’t work properly. This is called ‘homologous repair deficiency,’ or ‘HRD.’ These mutations include ‘’BRCA1,’ ‘BRCA2,’ ‘ATM,’ ‘ATR,’ ‘RAD 51,’ and ‘PALB2.’ You can find more information about the different mutations that affect the risk of ovarian cancer at:
facingourrisk.org/understan...
If one or more of the other repair proteins is already not working properly, disrupting PARP as well can have a greater effect. This is why PARP inhibitors are often effective in people with HRD, including those with BRCA mutations.
Because PARP inhibitors are a new type of treatment, there’s a lot of ongoing research into how they can be used, including in combination with other drugs. For example, studies have looked into giving PARP inhibitors together with chemotherapy, instead of chemotherapy and in combination with other targeted therapies such as Avastin or other immunotherapy drugs.
Ovacome participates in appraisal processes, when national organisations consider whether to make new treatment combinations available. Where possible, we include the experiences of people who have taken the drug in our submissions to help understanding of the wider benefits. We will post in the forum if we’re looking for people with experience of these drugs and combinations to help with our submissions.
You can find more information about PARP inhibitors at:
macmillan.org.uk/cancer-inf...
macmillan.org.uk/cancer-inf...
about-cancer.cancerresearch...
If you would like to share your experiences of PARP inhibitors or have any tips on them, please comment on this post. If you would like information or support, please contact our Support Line on 07503 682 311 or email support@ovacome.org.uk.
Best wishes
Julia (Ovacome Support Services Officer)
Parp inhibitors 
Maintenance therapies?
