Moderator of 1 Session
Presenter of 4 Presentations
PANEL 1: POTENTIAL IMPACT ON STANDARD OF CARE: REVIEW OF PENDING TRIALS (25 min) – moderated by Amit Oza
Panel Discussion
- Robert L Coleman (United States of America)
- Paul A. DiSilvestro (United States of America)
- Antonio Gonzalez-Martin (Spain)
- Thomas J. Herzog (United States of America)
- Mansoor R. Mirza (Denmark)
- Bradley J. Monk (United States of America)
- Kathleen N. Moore (United States of America)
- Amit Oza (Canada)
- Isabelle L. Ray-Coquard (France)
- Brian M. Slomovitz (United States of America)
- Jonathan A. Ledermann (United Kingdom)
• Overcoming PARP resistance
SEMINAL ABSTRACT PRESENTATION: OVERALL SURVIVAL RESULTS FROM THE PHASE 3 ARIEL4 STUDY OF RUCAPARIB VS CHEMOTHERAPY IN PATIENTS WITH ADVANCED, RELAPSED OVARIAN CARCINOMA AND A DELETERIOUS BRCA1/2 MUTATION
Abstract
Objectives
Rucaparib significantly improved progression-free survival (PFS) vs chemotherapy (CT) in patients with relapsed, heavily pretreated, BRCA1/2-mutated ovarian carcinoma in ARIEL4 (NCT02855944; Kristeleit et al. Lancet Oncol. 2022;23:465-78). We present final overall survival (OS) and PFS on the subsequent line of therapy (PFS2) data.
Methods
Patients were randomized 2:1 to oral rucaparib 600 mg BID or CT. In the CT group, patients with platinum-resistant (progression-free interval [PFI] ≥1 to <6 months) or partially platinum-sensitive (PFI ≥6 to <12 months) disease received weekly paclitaxel; those with fully platinum-sensitive disease (PFI ≥12 months) received investigator’s choice of platinum-based CT (single-agent platinum or platinum doublet). Patients allocated to CT could cross over to receive rucaparib upon confirmed radiographic progression per RECIST. OS was a standalone secondary endpoint; PFS2 was exploratory.
Results
As of data cutoff, 14/233 (6%) rucaparib-group and 0/116 CT-group patients were ongoing on assigned study treatment; 80 (69%) patients crossed over to receive rucaparib. Overall, 313/349 (90%) patients received rucaparib from randomization or after crossover. Death events have occurred in 244 (70%) patients. Efficacy endpoints are presented in the Table. Rucaparib safety was consistent with previous reports.
Conclusions
PFS2 did not significantly differ between treatment groups, while OS favored CT in the intent-to-treat (ITT) population. OS was similar between treatment groups amongst patients with platinum-sensitive disease; the difference in OS in the ITT population was driven by the platinum-resistant subgroup. The high rate of crossover confounded OS, highlighting important questions about PARP inhibitor sequencing in the treatment of advanced ovarian carcinomas.