Coleman and Brown Review Advancing Applications for PARP Inhibition in Ovarian Cancer

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Dr. Coleman and Dr. Brown discuss how understandings of BRCA and patient eligibility for PARP inhibitors have evolved in ovarian cancer, the effects of frontline maintenance trials on treatment recommendations, the clinical significance of the findings from the ARIEL4 trial, and where PARP inhibition is headed in the field.

Welcome to OncLive On AirTM! I’m your host today, Caroline Seymour.

OncLive On AirTM is a podcast from OncLive, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

In today’s episode, sponsored by Clovis Oncology, we had the pleasure of speaking with Robert L. Coleman, MD, FACOG, FACS, chief scientific officer of The US Oncology Network, and Jubilee Brown, MD, a professor and associate director of Gynecologic Oncology at the Levine Cancer Institute, of Atrium Health, to discuss BRCA positivity and the use of PARP inhibitors in patients with ovarian cancer following an announcement that the confirmatory ARIEL-4 study met its primary end point.

In December 2020, Clovis Oncology released a statement indicating that rucaparib (Rubraca) was found to result in a statistically significant improvement in progression-free survival (PFS) compared with chemotherapy in patients with BRCA-mutant ovarian cancer who had previously received 2 or more lines of chemotherapy in the phase 3 ARIEL4 trial (NCT02855944).

At the 2021 SGO Virtual Annual Meeting on Women’s Cancer, primary findings from the ARIEL4 trial were presented. The results showed that the investigator-assessed median PFS in the efficacy population was 7.4 months with rucaparib vs 5.7 months with chemotherapy.

Among the 23 patients with a BRCA reversion mutation, the median PFS in the rucaparib arm was 2.9 months vs 5.5 months in the chemotherapy arm.

The median duration of response in the efficacy population was 9.4 months with rucaparib vs 7.2 months with chemotherapy.

In December 2016, rucaparib was approved by the FDA for the treatment of patients with advanced ovarian cancer who have a deleterious BRCA mutation and have been treated with 2 or more chemotherapy regimens. The indication received an accelerated approval based on 2 multicenter, single-arm phase 1/2 clinical trials.

The ARIEL4 trial was designed to be the confirmatory phase 3 trial to further prove the benefit of rucaparib for this indication and was created in consultation with the FDA and the European Medicines Agency.

In our exclusive interview, Coleman and Brown explained how understandings of BRCA and patient eligibility for PARP inhibitors has evolved in ovarian cancer, discussed the effects of frontline maintenance trials on treatment recommendations, detailed the clinical significance of the findings from the ARIEL4 trial, and forecasted where PARP inhibition is headed in the field.

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