Patients with ovarian cancer responsive to platinum-based chemotherapy may experience a prolongation of progression-free survival (PFS) with rucaparib maintenance therapy, according to a study published in The Lancet. 1
Rucaparib is a poly(ADP-ribose) polymerase inhibitor that demonstrated anticancer activity in ovarian cancer with BRCA mutation or high percentage of genome-wide loss of heterozygosity. For the phase 3 ARIEL3 trial (ClinicalTrials.gov Identifier: NCT01968213), investigators evaluated the effect of rucaparib vs placebo among patients who had responded to second-line or later platinum-based chemotherapy.
Researchers randomly assigned 564 patients to receive oral rucaparib 600 mg twice daily or placebo. Eligible patients had platinum-sensitive malignancies, had at least 2 previous platinum-based therapies, and had reached complete or partial response to the most recent platinum-based regimen. Patients were also stratified into 3 cohorts based on genetic mutations.
Median PFS among patients with ovarian cancer characterized by BRCA-mutations was 16.6 months (95% CI, 13.4-22.9) in the rucaparib arm vs 5.4 months (95% CI, 3.4-6.7) among patients in the placebo arm (hazard ratio [HR], 0.23; 95% CI, 0.16-0.34; P < .0001).
Patients with homologous recombination deficient carcinoma treated with rucaparib had a PFS of 13.6 months (95% CI, 10.9-16.2) vs 5.4 months (95% CI, 5.1-5.6) in patients receiving placebo (HR, 0.32; 95% CI, 0.24-0.42; P < .0001).
Among patients without gene mutations in the intent-to-treat cohort, PFS in the rucaparib arm was 10.8 months (95% CI, 8.3-11.4) vs 5.4 months (95% CI, 5.3-5.5) in the placebo arm (HR, 0.36; 95% CI, 0.30-0.45; P < .0001).
Grade 3 or greater treatment-emergent adverse events (AE) were reported in 56% of patients receiving rucaparib and 15% in patients receiving placebo.
The authors conclude that “ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy.”
- Coleman RL, Oza AM, Lorusso D, et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Sep 12. doi: 10.1016/S0140-6736(17)32440-6 [Epub ahead of print]