The results of the ARIEL-4 clinical study report significant clinical benefits from rucaparib treatment compared to standard of care chemotherapy in BRCA-mutated advanced relapsed ovarian cancer patients. The findings of this phase-3 study were recently published in the journal The Lancet Oncology.
Only a few prospective studies have evaluated the efficacy of PARP inhibitors such as rucaparib versus platinum and non-platinum-based chemotherapies in BRCA1/2 mutated ovarian cancer patients. The ARIEL-4 study has compared PARP inhibitors to standard chemotherapies in this clinical setting.
The randomised, open-label, multicentre, international ARIEL-4 study enrolled 349 high-grade ovarian cancer patients with BRCA1/2 mutations who had received ≥2 previous chemotherapy regimens. The participants were randomised (2:1) to receive rucaparib (n=233, 600 mg, twice daily) or standard of care chemotherapy (n=116, administered per institutional guidelines), respectively. The study’s primary endpoint was investigator-assessed progression-free survival (PFS), and secondary end point’s included objective response rate (ORR) and safety.
After a median follow up of 25 months, rucaparib significantly prolonged the median PFS 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) than those who received chemotherapy. However, PFS benefits were not seen in patients with BRCA reversion mutations with rucaparib (n=13, 2.9 vs 5.5 months; HR, 2.769) treatment versus chemotherapy (n=10). Also, ORR was similar in both the treatment arms. The observed adverse events were consistent with the known safety profiles of rucaparib and chemotherapy.
The findings of the ARIEL-4 study demonstrate the efficacy of rucaparib as an alternative therapy for the treatment of BRCA1/2 mutated ovarian cancer patients.
Kristeleit R, Lisyanskaya A, Fedenko A, Dvorkin M, 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 Apr;23(4):465-478. doi: 10.1016/S1470-2045(22)00122-X.