From 1st February 2017, olaparib is available on the Pharmaceutical Benefits Scheme (PBS) for the treatment of relapsed platinum-sensitive high-grade serous ovarian, fallopian tube, and primary peritoneal cancer. Olaparib is an orally active inhibitor of poly (adenosine diphosphate-ribose) polymerase (PARP) enzymes. Tumours with BRCA1 and BRCA2 gene mutations rely on alternative DNA repair pathways, of which the PARP enzymes are important mediators. Olaparib treatment of these tumours results in inhibition of DNA repair and induction of cancer cell death.

Clinical trials demonstrate a significant improvement in progression-free survival (PFS) in olaparib-treated patients. A randomised, double-blind, phase II study of 265 participants showed a PFS of 8.4 months in the olaparib group compared to 4.8 months in the placebo group. The results also show an increase in overall survival, although this was not considered statistically significant.

The most common adverse effects associated with olaparib therapy include nausea, fatigue, diarrhoea, headache, reduced appetite, and anaemia. Other haematological toxicities necessitate the completion of full blood examinations at baseline and monthly during the first year of therapy.

Research is continuing into the potential benefit of olaparib for other PARP-dependent tumours such as gastric cancer, pancreatic cancer, and breast cancer. The US Food and Drug Administration (FDA) recently granted Breakthrough Therapy designation to olaparib for the treatment of prostate cancer following favourable results from the TOPARP-A trial.

References:

  1. Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012; 366: 1382-92.
  2. Lynparza(olaparib) Australian approved product information. Macquarie Park: AstraZeneca. Approved October 2016.
  3. Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, et al. DNA-repair defects and olaparib in metastatic prostate cancer. N Engl J Med. 2015; 373(18): 1697-1708.

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