The drugs called PARP inhibitors have been increasing discussed in the world of prostate cancer. There is every good reason to believe that we will continue to hear more about them and for certain select men with prostate cancer they will probably become a part of their treatment.
In a recent paper published in the New England Journal of Medicine there are detailed data about the activity of one of these PARP inhibitors, olaparib, in the treatment of select men with metastatic, castration-resistant prostate cancer (mCRPC).
In the paper by Mateo et al., (DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer describes a phase II clinical trial of the PARP inhibitor olaparib (Lynparza/AstraZeneca) used to treat 50 men with mCRPC post docetaxel and post either abiraterone or enzalutamide (in addition 58% of the subject men had also had prior use of the chemotherapy drug cabazitaxel.
The study showed that despite all the other drug failures 33 percent (16) of the men still had a response to the olaparib. Of the 16 responders 12 had a response that lasted 6 months or longer.
When they analyzed which men were the responders they found out that the men who had defects in their DNA-repair genes had a high response rate to the treatment drug olaparib. These genetic defects included homozygous deletions, deleterious mutations, or both in DNA-repair genes (e.g., the BRCA1/2 genes and others).
The unanswered question is, what effect, if any, could olaparib have on men who are at a much earlier disease stage. The men in this study were all very ill and their survival advantage was significantly limited by their very late disease stage. Could earlier use of drugs like olaparib provide a meaningful survival advantages to men with these mutated DNA-repair genes?