Maintenance Therapy with PARP Inhibitor Delays Ovarian Cancer Progression

June 2011, Vol 2, No 3 -

Chicago, IL—The oral poly ADP-ribose polymerase (PARP) inhibitor olaparib given as maintenance therapy delayed the time to tumor progression in patients with relapsed ovarian cancer, according to findings from an international study reported at ASCO 2011.

Jonathan Ledermann, MD, of University College London, United Kingdom, who presented the results, announced, “Olaparib significantly prolonged progression-free survival by nearly 4 months on average compared with placebo. This shows proof of principle for the concept of maintenance therapy in ovarian cancer using a PARP inhibitor.” The overall survival analysis is not yet mature.

Olaparib targets DNA repair weakness in tumors by inhibiting base excision repair through a defect known as homologous repair deficiency. The drug has already proved effective in patients with the BRCA gene mutations, which are often seen in patients with ovarian cancer, Dr Ledermann noted.

This phase 2 randomized, placebocontrolled study investigated the use of olaparib as maintenance therapy in patients with relapsed serous ovarian cancer who had responded to at least 2 previous platinum regimens (ie, were platinum-sensitive). Patients were randomized to oral olaparib 400 mg twice daily (N = 136) or placebo (N = 129).

Disease progression occurred in 44% of the olaparib arm versus 72% of the placebo arm; median progression-free survival rates were 8.4 months and 4.8 months, respectively, which translated to a very significant 65% risk reduced for disease progression.

“Our progression-free survival difference was very impressive and better than we anticipated,” Dr Ledermann commented. At the time of analysis, 50% of the patients treated with olaparib versus 16% of those receiving placebo were still being treated.

Olaparib was well tolerated and toxicities were consistent with those seen in previous studies, although there was a significant increase in nausea, fatigue, and vomiting with the active drug. Further studies will help determine the drug’s role in the routine treatment of ovarian cancer, he added.

Mark G. Kris, MD, Chair of ASCO’s Cancer Communications Committee, commented at a press briefing that the study is “important for 2 reasons.”

  • “First, the study fulfills a previously unmet need for women fighting ovarian cancer, that is, it lengthens the time that the disease is controlled after successful initial treatment. This translates usually into normal or near-normal quality of life. The study showed that olaparib can actually help do this,” he said.
  • Second, he added, the study shows the potential for targeted therapy to be effective based on exploiting a particular defect in the cancer cells’ ability to repair themselves.