In an article in The Lancet Oncology, Oza et al presented the final overall survival analysis of the phase III ARIEL trial of rucaparib vs standard-of-care chemotherapy in patients with relapsed BRCA-mutated ovarian carcinoma.
Study Details
In the open-label trial, 349 patients from sites in 12 countries were randomly assigned 2:1 between March 2017 and September 2020 to receive rucaparib (n = 233) or chemotherapy (n = 116). The primary analysis of the trial showed significant improvement in progression-free survival with rucaparib. Patients in the chemotherapy group were permitted to cross over to receive rucaparib after progression on chemotherapy.
Key Findings
Median follow-up was 41.2 months (interquartile range = 37.8–44.6 months) at data cutoff for the final overall survival analysis. A total of 80 (69%) of 116 patients in the chemotherapy group received rucaparib after disease progression.
In the intention-to-treat populations, median overall survival was 19.4 months (95% confidence interval [CI] = 15.2–23.6 months) in the rucaparib group vs 25.4 months (95% CI = 21.4–27.6 months) in the chemotherapy group (hazard ratio [HR] = 1.3, 95% CI = 1.0–1.7, P = .047).
In analysis excluding chemotherapy group patients who received rucaparib, median overall survival was 19.4 months (95% CI = 15.2–23.6 months) in the rucaparib group vs 9.1 months (95% CI = 7.0–18.1 months) in the chemotherapy group (HR = 0.42, 95% CI = 0.28–0.65, P < .0001).
No new safety signals were observed. Overall, the most common grade 3 to 4 adverse events across treatment groups included anemia/decreased hemoglobin (25% of rucaparib group vs 6% of chemotherapy group) and neutropenia/decreased neutrophils (11% vs 14%). Serious adverse events were reported in 28% vs 12% of patients.
The investigators concluded: “These data highlight the need for a better understanding of the most appropriate treatment for patients who have progressed on a poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor, and the optimal sequencing of chemotherapy and PARP inhibitors in advanced ovarian cancer.”
Amit M. Oza, MD, of Princess Margaret Cancer Centre, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Clovis Oncology. For full disclosures of the study authors, visit www.thelancet.com.
