ARIEL4: An international, randomised phase 3 study of the PARP inhibitor rucaparib vs chemotherapy for the treatment of BRCAmutated, relapsed, high-grade ovarian cancer

Background: Approximately 18%of patients (pts)with high-grade epithelial ovarian cancer (OC) harbour a deleterious germline BRCA1 or BRCA2 (BRCA1/2)mutation, and ≈7%harbour a somatic BRCA1/2mutation (Pennington et al. Clin Cancer Res. 2014;20:764-75). The poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib is approved in theUnited States for the treatment of pts with deleterious BRCAmutation (germline and/or somatic) associated advancedOCwho have been treated with≥2 chemotherapies. Data comparing PARP inhibitors to standard of care (SOC) treatment for relapsedOCare limited. Randomised studies are needed to assess the benefit-risk profile of PARP inhibitors vs SOC as treatment for BRCA1/2-mutated, relapsed, high-gradeOC. Trial design: ARIEL4 (EudraCT 2016-000816-14; NCT02855944) is evaluating rucaparib vs SOC chemotherapy as treatment for pts (n≈345) with relapsed, high-grade OC (regardless of histology) and a deleterious germline or somatic BRCA1/2 mutation who received ≥2 prior chemotherapy regimens. Pts stratified by progression-free interval after their most recent platinum regimen will be randomised 2:1 to receive rucaparib (600 mg BID) (n≈230) or chemotherapy (n≈115). Pts with platinum-resistant (progressive disease [PD] ≥1 to<6mo after last platinum) or partially platinumsensitive disease (PD≥6 to<12 mo after last platinum) will receive rucaparib or weekly paclitaxel; pts with platinum-sensitive disease (PD≥12 mo after last platinum) will receive rucaparib or platinum-based therapy (single-agent or doublet, per investigator discretion). Pts receiving chemotherapy have the option to cross over to rucaparib upon radiographic disease progression. The primary endpoint is investigatorassessed progression-free survival (RECIST version 1.1). Secondary endpoints include overall survival, objective response rate, RECIST/CA-125 response, duration of response, and patient-reported outcomes. Safety will be summarised descriptively using standard adverse event reporting.