Olaparib Shows Response Against Some Treatment-Resistant Prostate Cancers

A third of men with treatment-resistant advanced prostate cancer show promising clinical responses to olaparib, according to findings from the phase II TOPARP-A trial, the first published clinical study of a gene-targeted treatment for prostate cancer. The findings were published in TheNew England Journal of Medicine.¹

“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 tumours,” reported senior study author Johann de Bono, MD, PhD, of the Institute of Cancer Research, Royal Marsden NHS Foundation Trust, in Surrey, England. “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.”²

The study included 49 evaluable participants diagnosed with treatment-refractory, metastatic prostate cancer. The men were administered olaparib, a PARP inhibitor that targets expression of poly-ADP ribose polymerase, a DNA-repair enzyme. Study participants had been previously treated with docetaxel, abiraterone or enzalutamide, or cabazitaxel.¹

Next-generation sequencing showed that a third of the men in the study harbored mutations in DNA-repair genes, including BRCA1, BRCA2, ATM, CHEK2, and Fanconi’s anemia genes.¹ After treatment with olaparib tablets (400 mg twice daily), 14 of these 16 men (88%) demonstrated a RECIST 1.1 objective response or a ≥ 50% decrease in prostate-specific antigen levels, or a confirmed reduction in circulating tumor cell counts to less than five cells per 7.5 mL.

Consistent with previous studies of olaparib, anemia and fatigue were the most common grade 3 or 4 adverse events, affecting 20% and 12% of study participants, respectively.¹

Responses were seen in “all 7 patients with BRCA2 loss (4 with biallelic somatic loss, and 3 with germline mutations), and 4 of 5 with ATM aberrations,” the coauthors reported.¹    

Olaparib was initially developed and FDA-approved in 2014 to help treat women diagnosed with inherited BRCA mutations-related ovarian cancer.

“I hope it won’t be long before we are using olaparib in the clinic to treat prostate cancer, or before genomic stratification of cancers becomes a standard in this and other cancers,” Dr. de Bono said.

References:

• Mateo J, Carreira S, Sandhu S, et al. (2015). DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. The New England Journal of Medicine, Oct 29;373(18):1697-708. doi: 10.1056/NEJMoa1506859.
• The Institute of Cancer Research. (2015). Landmark clinical trial shows gene-targeted drug can treat prostate cancer.