A pioneering drug developed to treat women with inherited cancers, olaparib (AstraZeneca), can also benefit men with advanced prostate cancer, a major clinical trial concludes.
The trial, led by experts at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, is a milestone in cancer treatment as the first to show the benefits of ‘precision medicine’ in prostate cancer – with treatment matched to the particular genetic characteristics of a man’s tumour.
Olaparib was found to benefit as many as a third of patients with prostate cancer, including many who did not inherit cancer genes but whose tumours had acquired defects in DNA repair.
In the trial, called TOPARP-A, 49 men with treatment-resistant, advanced prostate cancer received olaparib, and 16 of them responded, as defined by a set of clinical criteria. Olaparib stopped prostate cancer growth, generating lasting falls in prostate specific antigen (PSA) levels, falls in circulating tumour cell counts in the blood, and radiological responses on CT scans and MRI.
The clinical trial found that up to 30% of men with advanced prostate cancer had tumours with defects in their systems for repairing DNA detected by genomic testing – and that these responded particularly well to olaparib. Of the 16 patients with detectable DNA repair mutations, 14 responded very well to olaparib – accounting for the large majority of those who benefited from the drug. Most of these men, who all had terminal prostate cancer with limited treatment options, had disease control lasting much longer than expected in this group of patients.
Olaparib could become a standard treatment option for advanced prostate cancer
The results have led on to the start of TOPARP-B, a second part of this trial in which only men whose prostate cancers have detectable DNA repair mutations will receive olaparib. If the results are successful, olaparib could become a standard treatment option for men with advanced prostate cancer and DNA repair mutations.
The drug, a type of treatment called a PARP inhibitor, was licensed last year for women with ovarian cancer and inherited BRCA mutations, but so far has not been approved for use on the NHS by NICE or the Cancer Drugs Fund.
Trial chief investigator Professor Johann de Bono, Head of Drug Development at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, said: “Our trial marks a significant step forward in the treatment of prostate cancer, showing that olaparib is highly effective at treating men with DNA repair defects in their tumours. It also proves the principle that we can detect prostate cancers with specific targetable mutations using genomic sequencing to deliver more precise cancer care by matching treatment to those men most likely to benefit.
“I hope it won’t be long before we are using olaparib in the clinic to treat prostate cancer, or before genomic stratification of cancers becomes a standard in this and other cancers.”
