A New Drug Affecting DNA Damage and Repair in Stage 4. Prostate Cancer Resistant to Standard Treatments: Olaparib (Lynparza)

According to a study in the respected NEJM, some advanced prostate cancer patients with damaged DNA repair genes who fail standard treatments respond very well to a new chemotherapy drug, Olaparib.

Previously, distant prostate cancer spread marked a helpless stage. Discovering androgens' role made androgen suppression standard for metastatic (advanced, stage 4.) disease. Initial responses are good, but genetic changes at androgen binding sites eventually cause resistance. Docetaxel chemotherapy, providing some survival benefit, is currently standard after androgen suppression resistance. No standard has yet been established when docetaxel fails or stops working. Strategies then principally aim to prolong life as much as possible. Options such as abiraterone exist, but survival rates remain low. New treatments are needed for metastatic, hormone-suppression-resistant prostate cancer. A recent NEJM study suggests Olaparib (Lynparza) as a candidate.

Also presented at the American Association for Cancer Research annual meeting, the study evaluated 49 patients resistant to hormonal and other standard treatments. Daily Olaparib was given and patients followed for 22 months. Among 49 patients, 17 responded: 6 showed tumor shrinkage on imaging, while 11 had PSA (prostate-specific antigen) reductions of at least %50. Responses lasted more than a year in 4 patients, exceeding 12 months. DNA repair gene defects were identified among 49 patients in 15, of whom 13 were responders. Thus, a significant relationship existed between these defects and Olaparib response.

Olaparib blocks PARB, an enzyme involved in DNA repair, targeting tumor cells sensitive to repair defects. It was approved in December 2014 for advanced ovarian cancer with BRCA defects. Effectiveness is now emerging in advanced prostate cancer with DNA repair defects too. Identifying sensitive groups matters not only for advanced ovarian and prostate cancers but other types. This study is important progress, but the small sample means it is only a beginning. Further supporting studies are needed before starting use in these patients.