Rucaparib prolonged progression-free survival (PFS) compared with standard-of-care chemotherapy in patients with BRCA-mutated, relapsed ovarian cancer, according to results of the phase 3 ARIEL4 trial.
Results from this trial (ClinicalTrials.gov Identifier: NCT02855944) were presented at the European Society for Medical Oncology (ESMO) Gynaecological Cancers Virtual Congress 2021.
“Rucaparib was approved as monotherapy for patients with BRCA-mutated, relapsed ovarian cancer who have received at least 2 lines of platinum-based chemotherapy following data from 2 early phase studies,” said presenter Rebecca Kristeleit, MD, of the Guy’s and St. Thomas’ NHS Trust in London, United Kingdom.
The ARIEL4 trial was designed in consultation with the U.S. Food and Drug Administration and the European Medicines Agency to confirm the efficacy and safety of rucaparib demonstrated in the earlier-phase trials.
ARIEL4 enrolled patients with relapsed, high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. Patients had received at least 2 prior chemotherapy regimens, including at least 1 platinum-based regimen, but no prior PARP inhibitor or single-agent paclitaxel treatment.
In all, 349 patients were randomly assigned to receive rucaparib (n=233) or standard chemotherapy (n=116). In the chemotherapy arm, patients who were fully platinum sensitive received single-agent or doublet platinum-based treatment, and patients who were partially sensitive or resistant to platinum therapy received paclitaxel.
Crossover was allowed for patients in the chemotherapy arm who experienced disease progression. At last follow-up, 44 patients in the rucaparib arm and 5 patients in the chemotherapy arm were still receiving study treatment.
Overall, PFS was superior with rucaparib. The median PFS was 7.4 months with rucaparib and 5.7 months with chemotherapy (hazard ratio [HR], 0.64; 95% CI, 0.49-0.84; P =.001).
However, patients with a BRCA reversion mutation had worse PFS with rucaparib than with chemotherapy. The median PFS was 2.9 months and 5.5 months, respectively (HR, 2.77; 95% CI, 0.99-7.76).
The objective response rate was 40.3% with rucaparib and 32.3% with chemotherapy (P =.13). The complete response rate was 4.7% and 2.1%, respectively. The median duration of response was 9.4 months and 7.2 months, respectively (HR, 0.59; 95% CI, 0.36-0.98).
Overall survival data are not yet mature. Patient-reported outcomes for global health status were similar between the treatment arms.
In general, the rucaparib arm had higher rates of treatment-emergent adverse events, including anemia, nausea, asthenia/fatigue, elevated liver enzymes, vomiting, abdominal pain, and thrombocytopenia. Rates of neutropenia, diarrhea, and alopecia were higher in the chemotherapy arm.
Treatment discontinuation due to adverse events occurred in 8.2% of patients in the rucaparib arm and 12.4% of those in the chemotherapy arm.
There were 5 cases of myelodysplastic syndromes/acute myeloid leukemia, all in the rucaparib arm.
Disclosures: This research was supported by Clovis Oncology, Inc. Dr Kristeleit declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Kristeleit R. Rucaparib vs chemotherapy in patients with advanced, relapsed ovarian cancer and a deleterious BRCA mutation: Efficacy and safety from ARIEL4, a randomized phase 3 study. Presented at: ESMO Gynaecological Cancers Virtual Congress; June 25-26, 2021.