PARP inhibitors are becoming well established in the management of some cancers, with further encouraging results in ovarian cancer presented this week. A role in prostate cancer is beginning to emerge, consequent to a subset of tumours having BRCA mutations or other genetic changes associated with deficient double-strand DNA break repair.
The PROfound study compared the PARP inhibitor Olaparib to the hormonal treatment options of Abiraterone or Enzalutamide in metastatic castrate refractory prostate cancer patients who had previous received Abiraterone or Enzalutamide. The results show a significant delay in progression when assessed by imaging, and a trend towards longer survival of around 3 months in the group of patients with defective DNA repair such as BRCA mutations who were treated with the PARP inhibitor rather than the hormone therapy. The toxicities were similar to what we have come to expect from Olaparib. The mechanisms of resistsnce to Abiraterone and Enzalutamide are complex and it isn’t clear if this choice of comparator was relevant. Thus, the results have to be taken with caution and I look forward to seeing them published in a peer-reviewed journal.