Olaparib for Ovarian Cancer, No Longer in Development

March 27, 2012 — The experimental PARP inhibitor olaparib for the treatment of ovarian cancer caused a stir at last year's annual meeting of the American Society of Clinical Oncology, because it showed a significant improvement in progression-free survival. The results of the study presented were published online today in the New England Journal of Medicine.

However, between the presentation and publication of the results, the company developing the olaparib, AstraZeneca, announced that it has dropped the ovarian cancer indication.

AstraZeneca told Medscape Medical News that although the company has decided not to develop olaparib as a maintenance therapy for serous ovarian cancer, it will evaluate development options for olaparib as an anticancer treatment, and the potential indications for BRCA1 and BRCA2 breast cancer are part of that evaluation.

The results just published come from a phase 2 study headed by Jonathan Ledermann, MD, director of services and professor of medical oncology at University College London in the United Kingdom, and colleagues. The trial was conducted in 265 patients with high-grade serous ovarian cancer, with or without BRCA1 or BRCA2 germ-line mutations, who had received 2 or more platinum-based regimens and had shown a partial or complete response to their most recent platinum-based regimen. Patients were randomized to receive either olaparib 400 mg twice daily or placebo.

Olaparib significantly improved median progression-free survival, compared with placebo (8.4 vs 4.8 months). The researchers note that recent studies of maintenance treatment in similar patient populations suggest that the progression-free survival seen in this placebo group is "in line with that expected."

However, at the interim analysis, this significant difference in progression-free survival did not translate into an overall survival benefit.

At the Society of Gynecologic Oncology 43rd Annual Meeting on Women's Cancer, held recently in Austin, Texas, Dr. Ledermann reported details of the interim analysis. It showed no difference in median overall survival between the olaparib and placebo groups (29.7 vs 29.9 months).

However, Dr. Ledermann explained that these data are not yet mature; deaths had occurred in 38% of patients. He noted that when the interim analysis was conducted, 21% of patients in the olaparib group and only 3% of patients in the placebo group remained in the study.

According to AstraZeneca, this is the main reason for its decision to discontinue the development of olaparib for serous ovarian cancer, because overall survival benefit "is the definitive measure of patient benefit in ovarian cancer."

In addition, attempts to identify a suitable tablet dose for use in phase 3 clinical trials was unsuccessful, the company said.

The study was funded by AstraZeneca. Dr. Ledermann has disclosed no relevant financial relationships. Several of his coauthors report receiving honoraria from various pharmaceutical companies, including AstraZeneca.

N Engl J Med. Published online March 27, 2012. Abstract

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