PARP Inhibitor Broadly Active in Ovarian Cancer

October 13, 2016 7:24 pm

The following article is provided by The Clearity Foundation to support women with ovarian cancer and their families. Learn more about The Clearity Foundation and the services we provide directly to women as they make treatment decisions and navigate emotional impacts of their diagnosis.

PARP Inhibitor Broadly Active in Ovarian Cancer

Maintenance therapy with a PARP inhibitor led to significant prolongation of progression-free survival (PFS) in patients with recurrent, platinum-sensitive ovarian cancer, a large placebo-controlled trial showed.

Median PFS approached 2 years in patients treated with niraparib as compared with 5.5 months for placebo-treated patients with germline BRCA mutations. Patients with non-BRCA disease had briefer PFS but still derived a similar magnitude of benefit when treated with the PARP inhibitor.

Niraparib-treated patients had higher rates of hematologic toxicity, but that did not lead to discontinuation in most cases, Mansoor R. Mirza, MD, of Rigshospitalet in Copenhagen, reported at the European Society for Medical Oncology conference.

“Niraparib significantly improved progression-free survival in patients with platinum-sensitive recurrent ovarian cancer, regardless ofBRCA mutation status,” Mirza said during a press briefing. “These landmark results warrant niraparib maintenance treatment for the whole study population.”

The findings were published online simultaneously in the New England Journal of Medicine.

The observation that patients benefited from niraparib regardless of BRCA status is a key finding that could influence use of the PARP-inhibitor class in the management of ovarian cancer, said Thomas Herzog, MD, of the University of Cincinnati.

“I think the fact that we’re growing a ‘pie,’ in terms of patients who are potentially eligible for PARP inhibition is important,” Herzog, who was not involved in the study, told MedPage Today. “That is the same strategy being developed with rucaparib, although the data are not out yet: Try to define a group of patients with homologous repair deficiency (HRD) who might benefit from PARP inhibition.

“People have been talking about the number of patients who might benefit from PARP inhibition, and now we’re starting to see it play out in real life. That is not only intriguing but promising for future development.”

The results continued a story that began with investigations of olaparib (Lynparza) as maintenance therapy in recurrent, platinum sensitive ovarian cancer. A phase II trial that supported the drug’s FDA approval showed more modest improvement in PFS but nonetheless a significant increase versus placebo-treated patients and consistency across a subgroup analysis.

PARP inhibitors target HRD, a defect in DNA repair that, if unchecked, allows cancer to grow, proliferate, and acquire the biological immortality that characterizes fatal ovarian cancer. Investigations initially focused on the subgroup of patients with germline BRCAmutations because of a known association with HRD. However, as data accumulated, a favorable effect on PFS was observed across other subgroups of patients with advanced ovarian cancer.

More recently, investigation has turned toward identifying patients with tumors exhibiting HRD, regardless of BRCA status. That scientific turn was incorporated into the design of the international, multicenter, randomized trial that Mirza reported.

“We hypothesized that niraparib … will provide a clinical benefit to all patients who have platinum-sensitive recurrent ovarian cancer who are in response to platinum, regardless of BRCA mutation status,” he said.

Investigators enrolled patients with platinum-sensitive, recurrent high-grade serous ovarian cancer. Platinum sensitivity was defined as complete or partial response, followed by lack of disease progression for more than 6 months after completing the last round of platinum therapy.

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