An important clinical trial reports that a drug already approved for the treatment of breast and ovarian cancer is more effective than targeted hormone therapy in controlling cancer in some patients with advanced prostate cancer.

Olapani is a drug without the side effects of chemotherapy, which can treat the Achilles' heel of prostate cancer, that is, a weak ability to repair damaged DNA. Now, it is about to be approved as the first gene-targeted therapy for prostate cancer.

This precise drug, called a PARP inhibitor, specifically targets cancer cells with defective DNA repair genes and prevents prostate cancer growth more effectively than the modern targeted hormone therapies abiraterone and enzalutamide.

The final results of this far-reaching trial, published in The New England Journal of Medicine today, herald the landmark approval of prostate cancer drugs in the United States and Europe this year. This study was funded by AstraZeneca.

A team of researchers from the London Cancer Institute and the Royal Marsden NHS Foundation, together with colleagues from around the world, including Northwestern University in Chicago, USA, studied 387 patients with advanced prostate cancer whose 15 DNA repair genes were altered. The researchers found that using olaparib in men with defects in this group of DNA repair genes significantly delayed the progression of the disease.

Prostate cancer patients with BRCA1, BRCA2, or ATM gene defects benefit most from treatment with olaparib, and they have a progression-free survival of 7.4 months compared with 3.6 months for patients taking enzalutamide and abiraterone.

Men with 12 additional preselected alterations in DNA repair genes also benefited from olaparib.

Overall, men with defects in any of the 15 DNA repair genes had an average of 5.8 months before their cancer worsened after using oraparib, compared with 3.5 months for men using targeted hormone therapy.

Abiraterone, discovered by the Cancer Institute (ICR) and developed by ICR and Royal Marsden, has changed the treatment of advanced prostate cancer.

The investigators are excited about the prospect of olaparib because ICR has discovered a genetically targeted approach and olaparib may be more effective than abiraterone in men with DNA repair mutations.

Men with BRCA1, BRCA2, or ATM gene defects had an overall survival of 19 months after treatment with olaparib, compared with 15 months after treatment with enzalutamide and abiraterone—although 80% of patients switched to olaparib after cancer progression and metastasis. However, longer follow-up is required to conclusively show an improvement in survival.

The most common adverse reactions were anemia and nausea. But overall, olaparib is a well-tolerated treatment that works much better for patients than chemotherapy.

PROfound is the first trial to show how important genetic testing is in prostate cancer patients. It is important to determine the treatment options for different patient populations based on their genes.

Researchers now hope that within the next two years, olaparib can be used to treat patients with advanced prostate cancer who have defective DNA repair genes.

In the next step, they will consider combining olaparib with other treatments with a view to further improving efficacy.

Johann de Bono, Professor of Experimental Cancer Medicine at the London Cancer Institute and Consultant in Medical Oncology at the Royal Marsden National Health Service Foundation, one of the study leaders, said: "Our findings suggest that olaparib, a drug that targets the Achilles heel of cancer cells without harming normal healthy cells, is more effective than targeted hormone therapy in some patients with advanced prostate cancer. It is exciting to see that a drug has been prolonging the lives of many patients with ovarian and breast cancer and now shows such a significant benefit in treating prostate cancer. I can't wait to see the drug start being applied to men who can benefit. In the next step, we will evaluate how to combine olaparib with other treatments to help men with prostate cancer and defective DNA repair genes live."