In patients with relapsed, platinum-sensitive high-grade ovarian carcinoma (HGOC) with germline or somatic BRCA mutations, treatment with rucaparib demonstrated activity with an acceptable safety profile, according to a pooled analysis presented at the 48th Annual Meeting of the Society of Gynecologic Oncology.1
Part 1 of the open-label, phase 2 ARIEL2 study (ClinicalTrials.gov Identifier: NCT01891344) showed that the poly (ADP-ribose) polymerase (PARP) inhibitor rucaparib was active in patients with relapsed, platinum-sensitive HGOC with a germline or somatic BRCA mutation. Part 2 evaluated rucaparib in patients who had received 3 to 4 prior lines of chemotherapy.
To evaluate the objective response rate and safety profile of rucaparib in this population, investigators of the ARIEL2 trial conducted a pooled analysis of parts 1 and 2. The researchers included only women who received a platinum agent as their last treatment and were sensitive to that treatment, and who had a somatic or germline BRCA mutation.
All participants received rucaparib 600 mg orally twice daily continuously in 28-day cycles until disease progression or unacceptable toxicity.
Results showed that 69.0% (95% CI, 55.5-80.5) of the 58 included patients achieved an objective response. Median duration of response was 9.2 months (95% CI, 6.4-12.9).
The study further demonstrated that 61.5% (95% CI, 40.6-
79.8), 90.0% (95% CI, 55.5–99.7), 75.0% (95% CI, 42.8–94.5), and 60.0% (95% CI 26.2–87.8) of women with a progression-free interval
of 6 to 9 months (n = 26), 9 to 12 months (n = 10), 12 to 18 months (n = 12), and greater than 18 months (n = 10) achieved an objective response, respectively.
The most frequently reported treatment-emergent adverse events were nausea, asthenia, vomiting, and anemia. Investigators observed no treatment-related deaths.
The US Food and Drug Administration granted accelerated approval to rucaparib in 2016 for the single agent treatment of patients with deleterious germline and/or somatic BRCA mutation associated advanced ovarian cancer who have been treated with 2 or more chemotherapies.
1. Konecny GE, Oza AM, Tinker AV, et al. Rucaparib in patients with relapsed, primary platinum-sensitive high-grade ovarian carcinoma with germline or somatic BRCA mutations: Integrated summary of efficacy and safety from the phase II study ARIEL2. Paper presented at: 48th Annual Meeting of the Society of Gynecologic Oncology; March 12-15, 2017; National Harbor, MD.