Longer-term outcomes for olaparib in the treatment of advanced castration-resistant prostate cancer

This study evaluated longer-term survival rates and the safety of olaparib (Lynparza) in patients with metastatic castration-resistant prostate cancer (mCRPC).

It found that treatment with olaparib led to significantly longer survival, especially in men with gene alterations.

CRPC is an especially aggressive form of prostate cancer (PC). Testosterone is a male sex hormone that triggers PC growth. A reduction in testosterone levels usually results in decreased growth. CRPC continues growing despite a drastic reduction of testosterone levels.

Another factor that indicates severe PC is confirmed BRCA1/BRCA2 or ATM gene alterations. Normal BRCA genes block the rapid and uncontrolled growth of cells, therefore the formation of tumors. The normal ATM gene sends signals to cells to control the rhythm they grow and divide. Abnormalities in these genes lead to the formation of tumors. 

The standard treatment for mCRPC includes enzalutamide (Xtandi) and abiraterone (Zytiga). Both drugs reduce hormones that are known to trigger PC growth. Olaparib is a targeted therapy that blocks a protein called PARP, which helps damaged cells to repair themselves. Therefore, olaparib keeps cancer cells from repairing themselves which eventually causes them to die.

Intermediate results comparing olaparib to enzalutamide or abiraterone in patients with mCRPC have shown a longer survival without cancer worsening with olaparib. However, the final results are yet to be presented.

The study included 387 patients with mCRPC and a gene alteration. 256 of these patients had an alteration in the BRCA1/BRCA2 or ATM genes. All patients had CRPC that continued to grow under previous treatment with enzalutamide and/or abiraterone. Some of them received chemotherapy prior to participation. They were randomly assigned to receive olaparib (group 1) or prednisone (Deltasone) with either abiraterone or enzalutamide. 

The average overall survival for group 1 was 17.3 months compared to 14 months for group B. Olaparib treatment was associated with a 21% lower risk of mortality compared to the control treatment. In patients with BRCA1/BRCA2 and ATM gene alterations, olaparib was associated with a 31% higher chance of a longer survival compared to the control.

66% of all patients in group 2 decided to change groups after confirmed progression. After including the patients who switched groups, olaparib treatment was associated with a 45% lower risk of mortality compared to the control group.

No new safety problems were reported in this final analysis. The most common side effects associated with olaparib treatment were anemia, nausea, fatigue, and decreased appetite.

The authors concluded olaparib improved survival in patients with mCRPC, particularly in those with BRCA1/BRCA2 or ATM gene alterations.

The study was supported by pharmaceutical companies AstraZeneca and Merck Sharp & Dohne, the manufacturers of olaparib.