Whitfield B. Growdon, MD, faculty member, Department of Obstetrics and Gynecology, director, Gynecologic Oncology Fellowship Program, NYU Grossman School of Medicine, expands on the decision to withdraw the later-line indication of olaparib (Lynparza) for patients with 

AstraZeneca and Merck voluntarily withdrew the indication for olaparib

-mutated ovarian cancer who received 3 or more prior lines of chemotherapy. This decision was based on updated findings from an overall survival (OS) subgroup analysis of the confirmatory phase 3 SOLO3 trial (NCT02282020) of patients with recurrent ovarian cancer who had measurable disease and a known germline 

 mutation, Growdon says. A signal from this analysis emerged, indicating that the use of this PARP inhibitor for this patient population may be associated with a decrease in efficacy, he reports.

Initial publication of data from SOLO3 showed that the trial met its primary end point of improved objective response rates (ORR) vs non-platinum chemotherapy, Growdon details. Prior analysis showed that the ORR generated by olaparib was 72% vs 51% for chemotherapy, and median progression-free survival was 13.4 months compared with 9.2 months in the chemotherapy group.

The final OS analysis of SOLO3 found that patients who received olaparib monotherapy had a median OS of 34.9 months after 48.9 months of median follow up, Growdon adds. Conversely, patients who were administered chemotherapy experienced a median OS of 32.9 months.

Notably, OS decreased by 10 months in patients who had received 3 or more prior lines of chemotherapy, although patients who had only received 2 prior lines of therapy still saw a minimal OS benefit. Growdon notes that this decision was surprising, as the trial had not been powered for OS and the changes observed were not statistically significant. However, the negatively trending hazard ratios observed led to the decision to remove the later-line indication for this agent, he concludes.

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Whitfield B. Growdon, MD, expands on the FDA’s decision to withdraw the later-line indication of olaparib for patients with BRCA-mutated ovarian cancer.

Whitfield B. Growdon, MD

Articles

Dr Growdon on the Withdrawal of Later-Line Indication For Olaparib in BRCA-Mutated Ovarian Cancer