Rucaparib a Winner for PFS, But Not for OS, in Recurrent Ovarian Cancer

NEW YORK — Rucaparib (Rubraca) turned in mixed results for survival outcomes in patients with recurrent ovarian carcinoma, according to an ARIEL3 trial update.

There was a benefit for progression-free survival (PFS), as treatment with the PARP inhibitor was tied to longer time-to-second disease progression (PFS2) in patients with BRCA-mutated disease (18.4 vs 26.1 months versus placebo) and among those with homologous recombination deficiency (HRD, 18.4 vs 24.7 months, respectively), reported Robert Coleman, MD, of MD Anderson Cancer Center in Houston.

And rucaparib boosted PFS2 in the intent-to-treat (ITT) population (20.6 vs 16.3, respectively), he said in a presentation at the International Gynecologic Cancer Society (IGCS) annual meeting.

But there was no improvement in the rates of overall survival (OS) among any patient subgroup, Coleman stated, although he added that these data were likely confounded by imbalance, and potential selection bias of subsequent treatments, which could not be controlled for post-trial.

In better news, rucaparib’s safety profile was consistent with previous findings based on this long-term follow-up, he said.

Oral rucaparib is approved in the U.S. and Europe as a maintenance therapy for patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer who had a complete or partial response to platinum-based therapy. While the drug is indicated for use as a maintenance therapy in patients with recurrent ovarian cancer, developer Clovis Oncology voluntarily withdrew its indication as a third-line treatment earlier in 2022, after negative OS findings from the ARIEL4 trial.

In the phase III ARIEL3 trial, rucaparib significantly improved PFS and post-progression outcomes in patients with platinum-sensitive, recurrent ovarian cancer. In the IGCS presentation, Coleman presented final OS results and other updated findings.

Patients were randomized to receive rucaparib (600 mg) or placebo with endpoints assessed across three cohorts: BRCA mutant, HRD, and ITT. Approximately 375 patients received rucaparib and 189 received placebo. Median follow-up was 6.4 years in both study groups.

Overall, 78% of patients who got rucaparib and 89% who received placebo underwent subsequent lines of therapy. Patients in the HRD and ITT groups had a median of three subsequent lines of therapy; the BRCA-mutated group had a median of two. Patients in the placebo group had a higher use of subsequent PARP inhibitor administration.

Rucaparib was favorable for PFS2 among three nested cohorts, but less impressive for OS, respectively:

• BRCA mutant: hazard ratio 0.67 (95% CI 0.48-0.94); HR 0.83 (95% CI 0.58-1.19)
• HRD: HR 0.72 (95% CI 0.56-0.92); HR 1.01 (95% CI 0.77-1.32)
• ITT: HR 0.70 (95% CI 0.58-0.85); HR 1.00 (95% CI 0.81-1.22)

As for adverse events, myelodysplastic syndromes/acute myeloid leukemia was reported in 3.8% of patients in the rucaparib group and 3.2% of patients in the placebo group.

Coleman emphasized that “these data provide robust support for the use of rucaparib as a maintenance therapy for recurrent, platinum-sensitive ovarian cancer.” He added that future studies will explore the impact of various subsequent lines of treatment on OS, as well as the overlapping mechanisms of platinum-based therapies and PARP inhibitors.