1 April 2021

The National Institute for Health and Care Excellence (NICE) recently approved the drugs olaparib plus bevacizumab (Avastin) for use within the Cancer Drugs Fund (CDF).

This provides a further option for maintenance treatment of stages 3 and 4 high-grade epithelial ovarian (including high grade clear cell and high grade endometrioid), fallopian tube or primary peritoneal cancer which has completely or partially responded to first-line platinum-based chemotherapy plus bevacizumab, and when the cancer is associated with homologous recombination deficiency (HRD).

The decision covers England, and NICE and CDF recommendations are also routinely followed by NHS Wales and usually by The Department of Health, Social Services and Public Safety (DHSSPS) in Northern Ireland as well.

This is the first time NICE have included HRD criteria in a decision about olaparib and so we thought it would be helpful to post some more information about HRD.

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 as part of the body’s growth and repair processes.  Sometimes copying errors are made. For this reason, our body regularly checks our DNA for damage and repairs it. If a cell’s DNA is not repaired properly, it can lead to cancer growth.

Homologous recombination is one of these repair processes. There are several different proteins involved in homologous recombination. You can watch a short animation about DNA damage and repair processes at 'What happens when your DNA is damaged?' - Monica Menesini (YouTube.) (The part about homologous recombination starts at 3 minutes, 20 seconds.)

If we have an altered gene for one of the proteins involved in homologous recombination, the protein might be missing or not work properly. This is called homologous recombination deficiency, or HRD. The BRCA1 and BRCA2 alterations, which increase the risk of breast and ovarian cancer, are two alterations which result in HRD. Others include ATM, ATR, RAD 51, and PALB2.

Another protein involved in DNA repair is called PARP. Olaparib is a type of drug called a PARP inhibitor and works by blocking the activity of PARP.

Cancers with HRD gene alterations often respond to treatment with PARP inhibitors, because the HRD means that one of the other repair proteins is already not working properly. Disrupting PARP as well can therefore have a greater effect in preventing the cancer repairing itself and continuing to grow.

Bevacizumab reduces the ability of cancers to form their own blood supply, which brings oxygen. It is thought that blocking PARP may be more effective when there is less oxygen in the tumour, so cancers associated with HRD may be more responsive to this combination of treatments.

Our support team are here to help with any queries you have, on 0800 008 7054 or [email protected] You can talk to your medical team about testing for HRD gene alterations.