Rucaparib Provides PFS Benefit vs Chemotherapy for BRCA1– or BRCA2–Mutant Ovarian Cancer

Among patients with BRCA1– or BRCA2–mutant ovarian cancer, treatment with the poly(adenosine diphosphate-ribose) polymerase (PARP)-inhibitor rucaparib was associated with statistically significant improvement in progression-free survival (PFS) compared to standard chemotherapy, according to results from the phase 3 ARIEL4 trial.

“Few prospective studies have compared…(PARP) inhibitors to chemotherapy for the treatment of BRCA1–mutated or BRCA2–mutated ovarian carcinoma. We aimed to assess rucaparib versus platinum-based and non-platinum-based chemotherapy in this setting,” wrote lead author Rebecca Kristeleit, MD, University College London Cancer Institute, UK, and coauthors.

The international, open-label study, recruited 349 patients between March 1, 2017, and September 24, 2020, from 64 hospitals and cancer centers across 12 countries (Brazil, Canada, Czech Republic, Hungary, Israel, Italy, Poland, Russia, Spain, Ukraine, the United Kingdom, and the United States). Eligible patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had to have received 2 or more previous chemotherapy regimens.

Patients were randomly assigned in a 2:1 ratio to rucaparib (n = 233) or chemotherapy (n = 116). Patients were stratified by PFS after the most recent platinum-containing therapy, to oral rucaparib (600 mg twice daily) or chemotherapy per institutional guidelines; patients with no more favorable than partially platinum-sensitive disease were given paclitaxel (starting dose 60–80 mg/m2 on days 1, 8, and 15), while those with fully platinum-sensitive disease received platinum-based chemotherapy (single-agent cisplatin or carboplatin, or platinum-doublet chemotherapy). Patients were treated in 21-day or 28-day cycles.

The data cutoff was September 30, 2020, and the median follow-up was 25 months (IQR 13.8 to 32.5).

In the efficacy population, median PFS was 7.4 months (95% CI 7.3 to 9.1) in the rucaparib group versus 5.7 months (5.5 to 7.3) in the chemotherapy group (hazard ratio [HR] 0.64 [95% CI 0.49 to 0.84]; P = .001).

In the intention-to-treat population, median PFS was 7.4 months in the rucaparib group compared with 5.7 months in the chemotherapy group (HR 0.67 [95% CI 0.52 to 0.86]; P = .0017).

There were 3 deaths considered to be potentially related to rucaparib: 1 due to cardiac disorder, 1 due to myelodysplastic syndrome, and another with an unconfirmed cause. Serious treatment-emergent adverse events occurred in 27% patients in the rucaparib group versus 12% in the chemotherapy group. Anemia or decreased hemoglobin occurred in 22% of patients in the rucaparib group versus 5% in the chemotherapy group.

Source:
Kristeleit R, Lisyanskaya A, 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. Published online March 14, 2022. doi:10.1016/S1470-2045(22)00122-X.