PARP Inhibitor Improves Survival in Ovarian Cancer

Olaparib improved median progression-free survival (PFS) by 65% in a phase II trial in women with recurrent ovarian cancer

Jonathan A. Ledermann, MD

Olaparib, an oral agent that is part of the promising PARP-inhibitor class of investigational drugs, improved median progression-free survival (PFS) by 65% in a phase II trial in women with recurrent ovarian cancer. The study was lauded in June at the ASCO meeting as the first randomized trial to establish the benefits of a PARP inhibitor as maintenance therapy in platinum- sensitive relapsed serous ovarian cancer, the most common form of the disease.

The study involved 265 patients who had received ≥2 platinum regimens, with 136 participants randomized to receive olaparib at 400 mg twice daily and 129 receiving placebo. The median PFS was 8.4 months in the olaparib arm versus 4.8 months in the placebo group (hazard ratio, 0.35; 95% confidence interval, 0.25-0.49; P <.00001).

“This is a very significant difference,” said Jonathan A. Ledermann, MD, principal investigator and professor of medical oncology at the UCL Cancer Institute in London, England.

Mark G. Kris, MD, chair of ASCO’s Cancer Communications Committee, said the trial is significant because it answers an unmet need for patients with ovarian cancer and it shows the “potential of targeted therapy.”

“That is our dream of personalized care and this is one example of that dream approaching reality,” Kris said.

The release of the olaparib study marked the second time in as many years that findings about a PARP inhibitor are generating excitement in clinical circles. Last year, phase II data regarding the use of iniparib in triple-negative breast cancer caused a sensation, but enthusiasm faded after disappointing phase III results were later released.


Dr. Pecora Discusses New PARP Inhibitor For Ovarian Cancer

Only on OncLive TV

The drugs work by inhibiting PARP, poly ADP ribose polymerase, an enzyme that helps cancer tumors repair DNA damage in cells.

The data from the olaparib study discussed at ASCO were “encouraging,” said Jane Robertson, MD, MBCHB, medical science director for the study at AstraZeneca, which sponsored the trial.

“Although it’s a small study, the hazard ratio is impressive,” she said in an interview.

Robertson said a phase II study of olaparib in combination with chemotherapy is underway in patients with ovarian cancer. AstraZeneca said results are expected in late 2011.

“We would have a much better idea of the best way to use olaparib in this disease” when those results are analyzed, said Robertson. “There is a rationale for its use as a monotherapy in this type of ovarian cancer. It has a more favorable tolerability profile compared with chemotherapy.”


Dr. Markman Discusses the Olaparib Phase II Trial

Only on OncLive TV

AstraZeneca said the majority of adverse events were grade 1 or 2 and that those more commonly reported with olaparib were nausea, fatigue, and vomiting. Ledermann said 50% of the patients in the olaparib group were still on the treatment at the time of the analysis. He also said the drug is being reformulated from a capsule into tablet form so patients will not have to take as many of the pills.

Up to 80% of ovarian cancer cases are diagnosed as the serous subtype, the most aggressive form of the disease. Robertson said it is “the type of [ovarian] cancer that’s more likely to have these DNA-damaged pathways.”

“It does tend to present in advanced stages,” she said, adding that it also responds to platinum- based chemotherapy and that, over time, fewer patients will respond to treatment for shorter periods.

Ledermann JA, Harter P, Gourley C, et al. Phase II randomized placebo-controlled study of olaparib (AZD2281) in patients with platinum-sensitive relapsed serous ovarian cancer. J Clin Oncol. 2011;29(suppl; abstr 5003).