Rucaparib Receives EC Approval for Advanced Ovarian Cancer

The European Commission (EC) has approved rucaparib (Rubraca) as first-line maintenance therapy for patients with advanced ovarian cancer, regardless of BRCA mutation status, who have responded following the completion of frontline platinum-based chemotherapy.¹

The regulatory decision was backed by findings from the ATHENA-MONO portion of the international, double-blind, phase 3 ATHENA trial (NCT03522246), in which rucaparib elicited a median progression-free survival (PFS) of 20.2 months (95% CI, 15.2-24.7) vs 9.2 months (95% CI, 8.3-12.2) with placebo (HR, 0.52; 95% CI, 0.40-0.68; log-rank P < .0001).² The PFS benefit with rucaparib was observed across all analyzed subgroups, including in patients with BRCA mutations (HR, 0.40; 95% CI, 0.21-0.75), BRCA wild-type/genetic loss heterozygosity (LOH)–high disease (HR, 0.58; 95% CI, 0.33-1.01), BRCA wild-type/LOH-low disease (HR, 0.65; 95% CI, 0.45-0.95), and BRCA wild-type/LOH-intermediate disease (HR, 0.39; 95% CI, 0.20-0.78). These findings were presented during the 2022 ASCO Annual Meeting and simultaneously published in the Journal of Clinical Oncology in June 2022.^1,2

Furthermore, in patients with homologous recombination deficiency (HRD) disease, the median PFS was 28.7 months (95% CI, 23.0-not reached) with rucaparib vs 11.3 months (95% CI, 9.1-22.1) with placebo (HR, 0.47; 95% CI, 0.31-0.72; log-rank P = .0004). In patients with HRD-negative disease, the median PFS was 12.1 months (95% CI, 11.1-17.7) with rucaparib vs 9.1 months (95% CI, 4.0-12.2) with placebo (HR, 0.65; 95% CI, 0.45-0.95).

“We are pleased to announce that the EC has granted approval, affirming rucaparib as a first-line maintenance treatment therapy for eligible patients with advanced ovarian cancer,” Frank Rotmann, founder and managing director of pharmaand GmbH (pharma&), stated in a press release.¹ “Today’s approval by the EC will help to ensure that health care providers and eligible patients, regardless of their BRCA mutation status, have access to and may benefit from rucaparib earlier in their treatment journey.”

“In the ATHENA-MONO trial, rucaparib prolonged PFS irrespective of molecular characteristics, and its approval by the EC as a first-line maintenance treatment is an important step forward in this difficult-to-treat population,” Rebecca Kristeleit, MD, PhD, a consultant medical oncologist and adjunct reader at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London in London, United Kingdom, as well as the European Network of Gynaecological Oncological Trial lead of the ATHENA trial, added in the release. “Women with advanced ovarian cancer need and deserve new treatment options to improve outcomes, and today’s approval is hopeful news for eligible patients in Europe.”

In 2018, the FDA approved rucaparib monotherapy as maintenance treatment for adult patients with recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer who experience a complete response (CR) or partial response (PR) to platinum-based chemotherapy.³ This regulatory decision was based on findings from the phase 3 ARIEL3 trial (NCT01968213).

ATHENA-MONO enrolled patients at least 18 years of age with newly diagnosed, histologically confirmed, advanced, high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancer.² Advanced disease was defined as stage III to IV disease per the International Federation of Gynecology and Obstetrics criteria. Patients were required to have completed cytoreductive surgery prior to chemotherapy or after neoadjuvant chemotherapy; completed and achieved an investigator-assessed response to 4 to 8 cycles of frontline platinum-doublet chemotherapy; a known BRCA mutation result of positive or negative via central testing; an ECOG performance status of 0 or 1; and adequate organ function.

Within 8 weeks of the first day of their last cycle of chemotherapy, patients were randomly assigned 4:1 to receive oral rucaparib or oral placebo plus intravenous (IV) placebo. Patients received oral rucaparib at 600 mg or placebo twice daily starting on day 1 of cycle 1, as well as IV placebo every 4 weeks beginning on day 1 of cycle 2 in 28-day cycles.

Investigator-assessed PFS per RECIST criteria served as the primary end point for ATHENA-MONO. Key secondary end points included overall survival; investigator-assessed overall response rate in patients with measurable disease at baseline; duration of response for patients with investigator-assessed confirmed radiographic CR or PR; and blinded independent central review (BICR)–assessed PFS per RECIST criteria.

The BICR-assessed PFS results were consistent with the investigator-assessed PFS results in the HRD population, overall population, and HRD subgroups.

The median duration of treatment was 14.7 months (range, 0.1-32.7) in the rucaparib arm vs 9.9 months (range, 0.9-25.9) in the placebo arm. Any-grade treatment-emergent adverse effects (TEAEs) occurred in 96.7% of patients in the rucaparib arm vs 92.7% of patients in the placebo arm. The most common TEAEs included nausea, asthenia, anemia, and increased alanine aminotransferase/aspartate aminotransferase.

Grade 3 or higher TEAEs occurred in 60.5% and 22.7% of patients in the rucaparib and placebo arms, respectively. In the rucaparib arm, the most common TEAEs of grade 3 or higher were anemia and neutropenia. In the placebo arm, the most common TEAE of grade 3 or higher was hypertension.

The safety profile of rucaparib that was observed in ATHENA-MONO was consistent with the current United States and European labels for the drug.¹

“Over the past 5 years, pharma& has firmly established itself as a globally integrated and agile company, with a focus on growing our portfolio of medicines and maintaining and developing the value of essential medicines for all who depend on them,” Elmar Zagler, founder and managing director of pharma&, added in the press release. “This approval by the EC marks another step toward delivering on that commitment, and we look forward to broadening access to the potential benefits of rucaparib to a wider group of eligible patients living with advanced ovarian cancer in Europe.”

pharma& does not recommend the use of rucaparib in patients with relapsed or progressive epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received prior treatment with a PARP inhibitor, as the efficacy of the agent in this population has not been investigated.

References

1. European Commission approves pharmaand GmbH’s Rubraca (rucaparib) as a first-line maintenance treatment in advanced ovarian cancer. News Release. Pharmaand GmbH. November 20, 2023. Accessed November 20, 2023. https://www.pharmaand.com/wp-content/uploads/2023/11/Rubraca-1st-line-aOC-EC-Decision-News-Release.pdf
2. A randomized, phase III trial to evaluate rucaparib monotherapy as maintenance treatment in patients with newly diagnosed ovarian cancer (ATHENA–MONO/GOG-3020/ENGOT-ov45). J Clin Oncol. 2022;40(34):3952-3964. doi:10.1200/JCO.22.01003
3. FDA approves rucaparib for maintenance treatment of recurrent ovarian, fallopian tube, or primary peritoneal cancer. News Release. FDA. April 6, 2018. Accessed November 20, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-rucaparib-maintenance-treatment-recurrent-ovarian-fallopian-tube-or-primary-peritoneal