A gene-targeted medicine, for breast and ovarian cancer, shows promise for some men with advanced prostate cancer, the results of a new clinical trial have shown.
More than 80% of men with advanced prostate cancer whose tumours had mutations in the BRCA genes responded well to treatment with olaparib, the research out today says.
The phase II TOPARP-B trial found that patients whose prostate cancers had DNA repair defects lived for more than 13 months on average when treated with olaparib. This increased to nearly 18 months among those with BRCA mutations.
TOPARP-B, led by a team at The Institute of Cancer Research, London, UK, and The Royal Marsden NHS Foundation Trust, is the first study to treat men whose prostate cancers had mutations in their DNA repair systems with olaparib. The findings are published in The Lancet Oncology.
The trial involved 98 men, at 17 UK hospitals, with mutations in DNA repair genes, and who all had advanced cancer which had been heavily pre-treated.
The team found that 47% with DNA repair defects – mostly in the BRCA1 and BRCA2 genes, but also other mutations were also detected including those in the PALB2, ATM and CDK12 genes – responded to olaparib, stopping disease progression for an average of 5.5 months.
More than 80% of men with BRCA mutations responded best to olaparib, 40% of whom remained free of disease progression for more than a year.
More than half of patients carrying PALB2 mutations also responded to olaparib, as well as 37% with ATM mutations and 20% with other DNA repair gene alterations.
The median overall survival with olaparib was 17.7 months for patients with BRCA mutations, compared with 16.6 for men with ATM mutations, and 13.9 months for those with PALB2 mutations.
The researchers say the results suggest men with advanced prostate cancer should now routinely have their tumours tested for DNA repair defects such as BRCA mutations- so that where appropriate they can benefit from PARP inhibitors.
Study leader Professor Johann de Bono, Regius professor of cancer research at The Institute of Cancer Research, London, and consultant medical oncologist at The Royal Marsden NHS Foundation Trust, said: “Our trial has shown that men with prostate cancer who were selected for faults in DNA repair genes responded very well to the targeted drug olaparib, especially where they had BRCA mutations in their tumours.
“This study and another phase III trial place olaparib on the verge of becoming the first genetically targeted treatment in prostate cancer. I’m excited by these findings, and keen to see further research assessing how we can combine olaparib with other treatments to extend patients’ lives even more dramatically.”
Professor Paul Workman, chief executive at The Institute of Cancer Research, London, added: “Precision medicines targeted to specific genetic faults are transforming treatment for many different cancers, and with this new research it looks like we will soon be able to add prostate cancer to that list. It’s exciting to see a drug which the ICR helped pioneer having such widespread benefits for both women and men with cancer.”
Lancet Oncology 3 December 2019
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