Results of the phase 3, randomized ARIEL4 trial demonstrate that patients with BRCA-mutated advanced, relapsed ovarian cancer derive significant progression-free survival benefit from rucaparib therapy compared with standard-of-care chemotherapy, with the emergence of no new safety signals.
The phase 3, randomized, open-label, international, multicenter ARIEL4 (NCT02855944) study compared the efficacy and safety of rucaparib versus standard-of-care chemotherapy in poly (ADP-ribose) polymerase (PARP) inhibitor–naïve patients with relapsed advanced ovarian cancer with deleterious BRCA mutations. The results of this study were reported at the 2021 Society of Gynecologic Oncology annual meeting.
The study enrolled patients with high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who had a deleterious BRCA1/2 mutation and had received ≥2 previous chemotherapy regimens. Eligible patients were randomized (2:1) to rucaparib (600 mg twice daily) or standard-of-care chemotherapy; stratification was based on progression-free interval (≥1 to <6 months [platinum resistant]; ≥6 to <12 months [partially platinum sensitive]; ≥12 months [fully platinum sensitive]). In the chemotherapy arm, platinum-resistant or partially platinum-sensitive disease cohorts received weekly paclitaxel 60 to 80 mg/m2, and the platinum-sensitive cohort received investigator’s choice of platinum-based chemotherapy (single-agent platinum, or platinum doublet). Both deleterious and reversion mutations were assessed. The primary end point was investigator-assessed progression-free survival; secondary end points included objective response rate (ORR) and safety. Efficacy outcomes were evaluated in the efficacy population (randomized patients with deleterious BRCA mutations, excluding BRCA reversion mutations) and the intent-to-treat (ITT) population (all randomized patients). The data cutoff date was September 30, 2020.
In the ITT population, 349 patients were randomized to rucaparib (n = 233) or chemotherapy (n = 116). Of these, 179 (51.3%) had platinum-resistant disease, 96 (27.5%) had partially platinum-sensitive disease, and 74 (21.2%) had fully platinum-sensitive disease. A total of 23 (6.6%) patients with BRCA reversion mutations, and 1 patient without a BRCA mutation were excluded from the efficacy population.
Median PFS was significantly prolonged with rucaparib (vs chemotherapy) in both the efficacy (7.4 vs 5.7 months; hazard ratio [HR], 0.64) and ITT populations (7.4 vs 5.7 months; HR, 0.67). In patients with BRCA reversion mutations, rucaparib treatment (n = 13) did not provide PFS benefit (2.9 vs 5.5 months; HR, 2.769) compared with chemotherapy (n = 10). In both populations, ORR was also similar between the rucaparib and chemotherapy arms. Adverse events were consistent with the known safety profiles of rucaparib and chemotherapy.
Results of the ARIEL4 trial demonstrate that patients with BRCA-mutated advanced, relapsed ovarian cancer derive significant PFS benefit from rucaparib therapy compared with standard-of-care chemotherapy, with the emergence of no new safety signals. The data also indicate that the presence of a BRCA reversion mutation predicts for primary resistance to rucaparib.
Source: Kristeleit R, Lisyanskaya A, Fedenko A, et al. Rucaparib versus chemotherapy in patients with advanced, relapsed ovarian cancer and a deleterious BRCA mutation: efficacy and safety from ARIEL4, a randomized phase III study. Gynecol Oncol. 2021;162(suppl_1):S3-S4.
