Olaparib maintenance therapy extended progression-free survival (PFS) in women with an aggressive form of platinum-sensitive ovarian cancer with a previous response to platinum-based chemotherapy. Women receiving olaparib lived a mean of 4 months longer and also had a longer time to disease progression than those who had no maintenance therapy. These were the conclusions of a phase 2 study published in the New England Journal of Medicine on April 12, 2012.
“Maintenance treatment with olaparib was associated with significant improvement in PFS in patients with platinumsensitive, relapsed, high-grade serous ovarian cancer. At this interim analysis, this did not translate into an overall survival benefit,” wrote the authors. They noted that 21% of patients in the maintenance arm were still on olaparib, indicating prolonged disease control in some patients. They also emphasized a need to identify biomarkers that could be used to select patients most likely to respond to treatment with a poly ADP ribose polymerase (PARP) inhibitor, such as olaparib, so that this therapy could be targeted to the appropriate population.
About 80% of patients with newly diagnosed ovarian cancer will respond to platinum-based chemotherapy, but most will relapse with only short-lived responses to subsequent lines of therapy. Maintenance therapy after response to first-line platinum-based therapy is an ongoing area of investigation to determine if response can be prolonged.
In the phase 2 trial, 265 patients were randomized to double-blind treatment with olaparib 400 mg BID or placebo. Median PFS was 8.4 months in the olaparib group versus 4.8 months with placebo, representing a 65% reduced risk of progression that was statistically significant (P <.001). The benefit of maintenance therapy was observed across all subgroups studied. Time to progression was also significantly longer in the group receiving olaparib: median 8.3 months versus 3.7 months for placebo, again a highly significant 65% reduction in risk of progression (P <.001).
The interim analysis reported in the New England Journal of Medicine found no significant difference between groups in overall survival: median 29.7 months for olaparib and 29.9 months for placebo.
The most commonly reported adverse events for olaparib versus placebo were nausea, 68% versus 35%; fatigue, 49% versus 38%; vomiting, 32% versus 14%; and anemia, 17% versus 5%, respectively. Most adverse events were grade 1 or 2.