Standard of Care Breakthrough in Platinum-Sensitive Ovarian Cancer

Submitted by admin5 on Thu, 09/14/2017 - 14:48

Patients with ovarian cancer who are responsive to platinum-based chemotherapy may experience more than double an increase in progression-free survival (PFS) with a specific maintenance therapy, regardless of their disease characterization.

Rucaparib is a poly ADP-ribose polymerase (PARP) inhibitor that has demonstrated anticancer activity in recurrent ovarian carcinoma exhibiting a BRCA mutation or high percentage of genome-wide loss of heterozygosity.

In a phase 3 trial (ARIEL3) led by Robert L Coleman, MD, department of gynecologic oncology and reproductive medicine, University of Texas MD Anderson Cancer Center, researchers investigated the effect of rucaparib vs placebo among patients with recurrent ovarian cancer who had responded to second-line or later platinum-based chemotherapy. A total of 564 patients were randomly assigned to receive oral rucaparib (600 mg twice daily) or placebo. Eligibility criteria for the study recruits included platinum-sensitive malignancies, at least two previous platinum-based therapies, and complete or partial response to the most recent platinum-based regimen.

Patients were stratified into three cohorts based on genetic mutations: BRCA, homologous recombination deficient carcinoma, or no observable mutations. Results of the study were published in The Lancet (online September 12, 2017; doi:10.1016/S0140-6736(17)32440-6).

Researchers reported that PFS among patients with BRCA-mutated disease was 16.6 months (95% CI, 13.4-22.9) in the rucaparib arm vs 5.4 months (95% CI, 3.4-6.7) in the placebo arm (HR, 0.23; 95% CI, 0.16-0.34; P < .0001).


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Similarly, PFS among patients with homologous recombination deficient carcinoma treated with rucaparib was 13.6 months vs 5.4 months with placebo. PFS among patients without gene mutations in the intent-to-treat cohort treated with rucaparib was 10.8 months vs 5.4 months with placebo.

Researchers acknowledged that grade 3 or higher adverse events were significantly higher in the rucaparib arm (56% vs 15% in the placebo arm).

Authors of the study concluded that, “ARIEL3 provides further evidence that use of a [PARP] 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.”—Zachary Bessette