Treatment with olaparib, a poly(adenosine disphosphate [ADP]-ribose) polymerase (PARP) inhibitor in patients with prostate cancer who no longer responded to standard treatments and who had defects in DNA-repair genes achieved a high response rate, a new study published in The New England Journal of Medicine has shown.1
For the phase 2 trial, researchers enrolled 50 patients with metastatic castration-resistant prostate cancer (mCRPC) who had received prior treatment with docetaxel. Of those, 49 and 29 had also received abiraterone or enzalutamide and cabazitaxel, respectively. All patients were treated with olaparib 400 mg orally twice daily.
Results showed that of the 16 evaluable patients with homozygous deletions, deleterious mutations, or both in DNA-repair genes, including BRCA1 and BRCA2, ATM, Fanconi’s anemia genes, and CHEK2, 88% achieved a response to olaparib treatment.
In regard to safety, the most common grade 3 or 4 adverse events were anemia and fatigue.
“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 tumors,” said chief investigator Professor Johann de Bono, head of drug development at The Institute of Cancer Research in England, and The Royal Marsden NHS Foundation Trust.
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“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.”
Olaparib is currently approved by the U.S. Food and Drug Administration for the treatment of patients with deleterious or suspected deleterious germline BRCA mutated advanced ovarian cancer who have been treated with at least 3 prior lines of chemotherapy.
- Mateo J, Carreira S, Sandhu S, et al. DNA-repair defects and olaparib in metastatic prostate cancer. N Engl J Med. 2015; 373:1697-1708.