Trial shows that olaparib, a poly ADP ribose polymerase inhibitor that is the first cancer drug to target an inherited genetic fault, can be used successfully to treat prostate cancers with a weakness in the ability to repair damaged DNA.
The conclusion of a major trial has found that a drug used to treat breast and ovarian cancers can extend the lives of some men with prostate cancer and should become a new standard treatment for the disease, according to research presented at the 2020 European Society for Medical Oncology Meeting.
The final results from the trial showed that olaparib, a poly ADP ribose polymerase inhibitor that is the first cancer drug to target an inherited genetic fault, can be used successfully to treat prostate cancers with a weakness in the ability to repair damaged DNA.
According to the research, the innovative drug was more effective than the modern hormone treatments abiraterone and enzalutamide at slowing down the growth and spread of prostate cancer in patients with advanced disease. Although the trial had already reported an improvement in disease development and outcome for this group of men with DNA repair faults in their tumors, the final results published at this stage offer a longer follow-up and conclusively demonstrate an improvement in survival for men who were given olaparib.
The trial studied 387 men with advanced prostate cancer who had defects in 1 or more of 15 DNA repair genes. Men whose tumor had genetic changes were assigned to 2 groups: 1 group for those with changes in BRCA1, BRCA2, or ATM, and another group for men with genetic changes in any other of the DNA repair genes studied. The men were then randomly assigned to olaparib or standard hormone therapy, according to the study authors.
The final analysis of data from the PROfound trial found that olaparib blocked prostate cancer growth more effectively than the modern targeted hormone treatments abiraterone and enzalutamide in men with faulty DNA repair genes. Further, patients with genetic alterations in the DNA repair genes BRCA1, BRCA2, or ATM who received olaparib had a median overall survival (OS) of 19.1 months compared with 14.7 months for those on targeted hormone treatments.
Meanwhile, patients with genetic alterations in any other of the DNA repair genes studied had an OS of 14.1 months with olaparib or 11.5 months with the targeted hormonal drugs, according to the study authors. During the trial, patients were allowed to switch treatments and start taking the experimental medication, olaparib, once their disease progressed.
Overall, 66% of men who received the targeted hormone treatments were switched to receive olaparib. The researchers analyzed the impact on survival of crossing over from targeted hormone treatments and found that those who switched to olaparib were less likely to die sooner.
“The FDA has already approved olaparib for prostate cancer in the US and I hope that the final results of our trial will bring the authorization of this innovative drug to Europe and the UK as soon as possible,” said study co-leader Johann de Bono, professor of Experimental Cancer Medicine at the Institute of Cancer Research, in a press release. “This will enable more men with the disease to take advantage of this targeted treatment so that they can have more precious time with their loved ones.”
ESMO 2020: Breast cancer drug set to transform prostate cancer treatment. The Institute of Cancer Research. https://www.icr.ac.uk/news-archive/esmo-2020-breast-cancer-drug-set-to-transform-prostate-cancer-treatment. Published September 20, 2020. Accessed September 21, 2020.