Revolutionizing Prostate Cancer Treatment With Olaparib

Systemic treatment options for advanced prostate cancer patients have evolved considerably in recent years with the introduction of several classes of novel therapeutics. Among the available options are poly(ADP-ribose) polymerase (PARP) inhibitors. Olaparib is a United States (US) Food and Drug Administration (FDA) approved PARP inhibitor for the treatment of metastatic castration-resistant prostate cancer which has failed prior hormonal treatment (also known as androgen deprivation therapy) with enzalutamide or abiraterone.

You will also need to take a test to check if you are suitable for the treatment, as it works best only if your tumor has specific errors in genes involved in DNA repair, in particular, the breast cancer susceptibility (BRCA) genes (e.g. BRCA1 and BRCA2, which are implicated in increased risk of certain cancers) and the Ataxia-telangiectasia mutated (ATM) gene. Up to 30% of patients are likely to have some errors of DNA repair in their tumors, with mutations in the BRCA genes being the most common.

Olaparib works by blocking critical DNA repair systems in cancer cells. PARP is one such enzyme protein which helps repair DNA damage in cancer cells. PARP inhibitors hence prevent this repair pathway. As cancer cells already have other defective repair mechanisms (genetic mutations), the addition of PARP inhibitors blocks cancer cells from repairing the damage done to their genetic material. Finally, this promotes cancer cell death resulting from the remaining DNA damage.

Below are some common side effects reported after taking olaparib. You will not experience all of these side effects, but there is a risk that you may encounter a few of these at the same time.

The side effects commonly reported in over 1 in 10 people include:

• Nausea, vomiting, diarrhea or indigestion
• Tiredness or weakness
• Low blood cell count (red blood cells, white blood cells or platelets)
• Loss of appetite or changes in the way food tastes
• Headaches or dizziness
• Shortness of breath or cough

• Nausea or vomiting is very commonly seen.

You should inform your doctor if you experience this so they can prescribe you medication to prevent vomiting.

• Your blood cell numbers will be monitored regularly — once before the start of your treatment and monthly during your treatment.

This is to monitor for warning symptoms of severe bone marrow issues. While rare, bone marrow cancer, which can be fatal, can occur in around 1.5% of patients taking olaparib. If your blood cell counts appear low, your doctor may decide, for your safety, to stop the treatment until they return to an acceptable level.

• You may experience lung inflammation, which should be monitored carefully.

Around 0.8% of those taking the drug experience this. If you experience new or worsening problems with shortness of breath, cough or wheezing, you should report this to your doctor. You may be requested to do a chest x-ray as a precaution.

• There is a chance of a blood clot developing in your legs or lungs.

Blood clot formation in the legs occurs in around 8% of patients taking olaparib. If you experience any issues with pain, swelling in your hands or feet, shortness of breath or faster than normal breathing or heart rate, you should inform your doctor quickly. They can then prescribe you a blood thinner to prevent blood clot formation if necessary.

• Due to the risk of fetal toxicity, if your partner is of reproductive potential, effective contraception should be used, up to three months after your last dose.

The approval of olaparib heralds a new beginning in treating advanced prostate cancer, introducing a more personalized approach to treating the disease. With new treatment combinations on the horizon, researchers remain hopeful in continuing to improve the outlook for advanced prostate cancer.