Olaparib improved PFS in relapsed ovarian cancer

In a phase 2 international trial, the poly ADP-ribose polymerase inhibitor olaparib extended PFS by 4 months in women with relapsed ovarian cancer.

Jonathan A. Ledermann, MD, professor of medical oncology at UCL Cancer Institute, University College London, discussed the results Wednesday during a press conference in advance of the 2011 ASCO Annual Meeting. If these results are confirmed in future trials, olaparib (AstraZeneca) could be used long term as maintenance therapy after standard chemotherapy, he said.

“Olaparib significantly prolongs the time patients live without experiencing tumor growth by nearly 4 months after the end of chemotherapy,” Ledermann said. “This is the first study to demonstrate a statistically significant benefit of maintenance treatment for platinum-sensitive, relapsed serous ovarian cancer.”

In the multicenter study, 136 women with high-grade serous ovarian cancer with and without BRCA1 or BRCA2 mutations were randomly assigned to 400 mg oral olaparib. Another 129 women were assigned to placebo. All patients had received at least two previous platinum regimens and were in a maintained partial or complete response since their last platinum-containing regimen.

Median PFS for the olaparib group was 8.4 months vs 4.8 months for placebo (HR=0.35; 95% CI, 0.25-0.47). Median time to progression also favored olaparib, 8.3 months vs 3.7 months.

“This is a very significant difference — a 65% improvement,” Ledermann said.

There were 153 (58%) progression events at data cutoff. OS data were too immature for analysis. Half of patients remained on olaparib at cutoff compared with just 16% in the placebo group.

Most common grade-3/grade-4 adverse events in the olaparib group were fatigue (nine patients) and anemia (seven patients) for olaparib. Thirty-one patients assigned to olaparib had both dose reductions and interruptions compared with nine patients in the placebo group. Three patients (2.2%) discontinued olaparib due to adverse events compared with one patient in the placebo group. – by Jason Harris

For more information:

Ledermann JA. #5003. To be presented at: 2011 ASCO Annual Meeting; June 3-7, 2011; Chicago.

This study is important for two reasons: First, it fulfills a previously unmet need for women fighting ovarian cancer by lengthening the time disease is controlled after the completion of successful initial therapy. Generally, disease control translates into a normal or near-normal life, which is really the goal of cancer therapy. Second, these results once again show the potential of targeted therapy. Scientists discovered the special characteristics of those ovarian cancer cells that would be specifically susceptible to disruption based on this type of treatment. They devised a treatment for a population of patients with a very specific defect in their cancers that exploited that defect and that lead to a longer life for patients with this disease. That is our dream for personalized care, and this is one example of that dream approaching reality.

– Mark G. Kris, MD
Chair, ASCO Cancer Communications Committee

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