Breast Cancer Drug Olaparib Outperforms Standard Hormonal Therapy in Prostate Cancer with DNA Repair Defects

May 26, 2020 /Bio ValleyBIOON /——An importantClinical TrialsThe report states that a drug already approved for the treatment ofBreast Cancerand ovarian cancer drugs are more effective than targeted hormone therapy in controlling cancer in certain patients with advanced prostate cancer.

Olaparib is a drug devoid of chemotherapy-related side effects that targets a critical vulnerability in prostate cancer—namely, its impaired ability to repair damaged DNA. It is now poised to become the first gene-targeted therapy approved for prostate cancer.

These precision drugs, known as PARP inhibitors, specifically target cancer cells with defective DNA repair genes and have been shown to inhibit prostate cancer growth more effectively than modern targeted hormonal therapies such as abiraterone and enzalutamide.

The final results of this landmark trial were published in the prestigious journal The New England Journal of Medicine Today, heralding a milestone approval for olaparib as a prostate cancer drug in the United States and Europe this year. This study was conducted byAstraZenecaFunding.

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A research team from The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, in collaboration with colleagues from institutions worldwide, including Northwestern University in Chicago, USA, studied 387 patients with advanced prostate cancer who had alterations in one or more of 15 DNA repair genes. The researchers found that treatment with olaparib significantly delayed disease progression in men with defects in this set of DNA repair genes.

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

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

Overall, men with defects in any one of the 15 DNA repair genes had a median time of 5.8 months before their cancer worsened after using olaparib, compared to 3.5 months for those receiving targeted hormone therapy.

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

Researchers are excited about the prospects of olaparib, as ICR has identified a gene-targeting approach suggesting that olaparib may be more effective than abiraterone in men with DNA repair mutations.

The overall survival of men with BRCA1, BRCA2, or ATM gene defects was 19 months after treatment with olaparib, compared to 15 months after treatment with enzalutamide and abiraterone—despite 80% of patients switching to olaparib after cancer progression and metastasis. However, longer follow-up is needed to ultimately demonstrate improved survival rates.

Most CommonAdverse ReactionsYesAnemiaand nausea. However, overall, olaparib is a well-tolerated treatment that offers significantly better therapeutic outcomes for patients compared to chemotherapy.

The PROfound trial was the first to demonstrate the critical importance of genetic testing in patients with prostate cancer. It is essential to tailor treatment strategies based on the genetic profiles of different patient populations.

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

Next, they will consider combining olaparib with other therapies in an effort to further improve efficacy.

One of the study leads, Professor of Experimental Cancer Medicine at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation TrustTumorMedical Advisor Professor Johann de Bono said:

“Our findings indicate that olaparib—a drug that targets the fatal weaknesses of cancer cells without harming normal, healthy cells—is more effective than targeted hormone therapy in certain patients with advanced prostate cancer. It is exciting to see a drug that has already extended the lives of many patients with ovarian and breast cancer now demonstrating such clear benefits in the treatment of prostate cancer. I am eager to see this drug begin to be applied to men who can benefit from it. Next, we will evaluate how to combine olaparib with other therapies to help men with prostate cancer and DNA repair gene defects live longer.”

Johann de Bono, a 59-year-old patient at The Royal Marsden Hospital, said:

"Initially, after my diagnosis, I received hormone therapy followed by chemotherapy. Six months after completing chemotherapy, my PSA levels rose rapidly, and my doctor told me that my chances of surviving two years were very low. I sought a second opinion at The Royal Marsden Hospital, where Professor Johann de Bono discovered that I had a genetic mutation making me eligible for the olaparib trial. I have been on the medication for nearly two years. Before starting treatment, I had extensive lymph node involvement."Tumor, but now I can only see one. I am very fortunate to have experienced no side effects."

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:

"It is gratifying to see this treatment approach, as we have learned how to target mutant genes"Gene Therapy, can successfully treat some patients with advanced prostate cancer. These landmark findings mean that olaparib will now become the first gene-targeted drug for treating this disease. The next step will be to find new ways to combine olaparib with other treatments to prevent or overcome resistance. The purpose of this research is to target the lethal adaptability and evolutionary capacity of cancer, and we will conduct this research at the Cancer Drug Discovery Center, which will open later this year." (Bioon.com)