Rucaparib significantly improved progression-free survival (PFS) compared with standard chemotherapy in heavily pretreated patients with BRCA-mutated, relapsed ovarian cancer, according to results of the phase 3 ARIEL4 trial published in The Lancet Oncology.
Rucaparib prolonged PFS across a broad population of patients with either somatic or germline BRCA mutations and those with platinum-resistant, partially platinum-sensitive, and fully platinum-sensitive ovarian cancer.
“To our knowledge, ARIEL4 is the first study to compare a PARP inhibitor with standard-of-care platinum and non-platinum-based chemotherapy in patients with germline or somatic BRCA1 or BRCA2 mutations and relapsed ovarian carcinoma,” the researchers wrote.
This open-label, phase 3 randomized controlled trial (ClinicalTrials.gov Identifier: NCT02855944) enrolled 349 patients with high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer with a germline or somatic BRCA1 or BRCA2 mutation who had received 2 or more previous chemotherapy regimens.
The median age of the patients was 58 years (interquartile range [IQR], 52-64), 95% were White, 51% were platinum-resistant, 28% were partially platinum-sensitive, and 21% were fully platinum-sensitive.
The participants were randomly assigned to receive 600 mg of oral rucaparib twice daily (233 patients) or chemotherapy (116 patients). In the chemotherapy arm, patients with platinum-resistant or partially platinum-sensitive disease were given paclitaxel, while those with fully platinum-sensitive disease were treated with platinum-based chemotherapy in 21- or 28-day cycles. The median follow-up was 25.0 months (IQR, 13.8-32.5).
In the intention-to-treat population (ITT), the median PFS was 7.4 months in the rucaparib arm and 5.7 months in the chemotherapy arm (hazard ratio [HR], 0.67; 95% CI, 0.52-0.86; P =.0017).
Researchers did not find a significant difference in the objective response rate between the 2 treatment arms (P =.13). However, the median duration of response was longer in the rucaparib arm (9.4 months) than in the chemotherapy arm (7.2 months; HR, 0.56).
Researchers said the OS data were not mature, with 51% of death events at the time of analysis. Patient follow-up is ongoing, and OS will be assessed when 70% maturity is reached.
A majority of treatment-emergent adverse events (TEAEs) were grade 1 or 2. Serious TEAEs were reported in 27% of patients in the rucaparib arm and 12% of patients in the chemotherapy arm. Serious AEs related to treatment were reported in 14% of patients in the rucaparib arm and 5% in the chemotherapy arm.
Treatment interruption and/or dose reduction due to TEAEs occurred in 50% of patients in the rucaparib arm and 44% of patients in the chemotherapy arm. There were 3 fatalities that were potentially related to rucaparib treatment — 1 due to cardiac disorder, 1 due to myelodysplastic syndrome, and 1 with an unknown cause.
“Results from the ARIEL4 study support rucaparib as an alternative treatment option to chemotherapy for patients with relapsed, BRCA1-mutated or BRCA2-mutated ovarian carcinoma,” the researchers concluded.
Disclosures: This research was supported by Clovis Oncology. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Kristeleit, Lisyanskaya, Fedenko A, et al. Rucaparib versus standard-of-care chemotherapy in patients with relapsed ovarian cancer and a deleterious BRCA1 or BRCA2 mutation (ARIEL4): An international, open-label, randomised, phase 3 trial. Lancet Oncol. 2022;23(4):465-478. doi:10.1016/S1470-2045(22)00122-X