On April 6, 2018, the FDA approved RUBRACA® (rucaparib), marketed by Clovis Oncology Inc., as a maintenance therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy . There are about 22,000 incidences of ovarian cancer per year in the United States (US) and ovarian cancer is the fifth leading cause of cancer-related deaths amongst US women . Standard frontline treatment for ovarian cancer is platinum-based chemotherapy; however, most patients who respond to treatment eventually relapse. Thus, there is a need for effective maintenance therapies that can prevent or prolong post-platinum relapse. Rucaparib is a poly(ADP-ribose) polymerase (PARP) inhibitor that works by preventing DNA repair in cells with homologous recombination deficiency (HRD) . It was previously approved in December of 2016 for the third-line treatment of patients with deleterious BRCA1 or BRCA2 mutation-positive ovarian cancer . BRCA1/2 proteins function as tumor suppressors by supporting homologous recombination, and therefore cells with dysfunctional BRCA1/2 proteins are sensitive to PARP inhibition .
The recent approval was based on the results of a randomized phase 3 trial, ARIEL3, assessing rucaparib as a maintenance therapy for patients with platinum-sensitive high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, who had received at least two prior platinum-based chemotherapy regimens (NCT01968213) . Patients were randomized 2:1 to receive rucaparib or placebo and were stratified based on BRCA1/2 mutation and HRD status. Median progression-free survival (mPFS) in the intent-to-treat population was doubled in patients receiving rucaparib over placebo, 10.8 vs. 5.4 months, respectively . Additional benefit was experienced by patients with BRCA1/2 mutant-positive or HRD-positive disease with a mPFS of 16.6 months and 13.6 months, respectively . The safety profile of rucaparib therapy was found to be tolerable with the most common grade 3 or 4 adverse events being anemia (19%) and increased liver enzymes (10%).
- RUBRACA® (rucaparib) tablets, for oral use. Drugs@FDA: FDA Approved Drug Products 04/06/2018 [cited 2018 May 3]; Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209115s003lbl.pdf.
- Siegel, R.L., K.D. Miller, and A. Jemal, Cancer Statistics, 2017. CA Cancer J Clin, 2017. 67(1): p. 7-30.
- Coleman, R.L., 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. 390(10106): p. 1949-1961.
- RUBRACA™ (rucaparib) tablets, for oral use Initial U.S. Approval: 2016 Drugs@FDA: FDA Approved Drug Products [cited 2018 May 3]; Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/209115s000lbl.pdf.
- Lee, J.M., J.A. Ledermann, and E.C. Kohn, PARP Inhibitors for BRCA1/2 mutation-associated and BRCA-like malignancies. Ann Oncol, 2014. 25(1): p. 32-40.
- A Study of Rucaparib as Switch Maintenance Following Platinum-Based Chemotherapy in Patients With Platinum-Sensitive, High-Grade Serous or Endometrioid Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancer (ARIEL3). ClinicalTrials.gov [cited 2018 May 3]; Available from: https://clinicaltrials.gov/ct2/show/NCT01968213.