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Joyce F. Liu, MD, MPH
Joyce F. Liu, MD, MPH
Posted: Monday, April 28, 2025
Patients with relapsed ovarian cancer and a deleterious BRCA1 or BRCA2 mutation responded better to chemotherapy than to the PARP inhibitor rucaparib (Rubraca) long term after prior chemotherapy regimens, according to the final results from the phase III ARIEL4 trial published in The Lancet Oncology. The study authors, led by Amit M. Oza, MD, of the Princess Margaret Cancer Centre and University Health Network in Toronto, Canada,and colleagues noted that progression-free survival had favored the rucaparib arm, but overall survival was better in the chemotherapy arm of the trial.
“These data highlight the need for a better understanding of the most appropriate treatment for patients who have progressed on a PARP inhibitor, and the optimal sequencing of chemotherapy and PARP inhibitors in advanced ovarian cancer,” the investigators wrote in their report.
Patients who had received at least two prior chemotherapy regimens were randomly assigned 2:1 to either the rucaparib arm (n = 233) or the chemotherapy arm (n = 116). In the rucaparib arm, patients received 600 mg of the PARP inhibitor twice daily in 28-day cycles. In the chemotherapy arm, patients received investigator’s choice of regimens according to platinum sensitivity. Crossover to the rucaparib arm was allowed at disease progression, and 69% of the chemotherapy arm crossed over.
As of the final analysis, the median overall survival at 41.2 months of follow-up (interquartile range = 37.8–44.6 months) in the intention-to-treat population was 19.4 months (95% confidence interval [CI] = 15.2–23.6 months) in the rucaparib arm vs 25.4 months (95% CI = 21.4–27.6 months) in the chemotherapy arm (hazard ratio = 1.3; 95% CI = 1.0–1.7; P = .047).
Crossover did not appear to impact safety signals, according to the investigators. Serious adverse events were reported in 28% of the rucaparib arm and 12% of the chemotherapy group. Treatment-related deaths were noted in 10 patients from the rucaparib group, with 2 considered to be related to treatment, and 1 treatment-related death was reported in the chemotherapy arm.
Disclosure: For full disclosures of the study authors, visit thelancet.com.
