Rucaparib - Second PARP inhibitor hits the market for ovarian cancer

March-April 2017 www.jcso-online.com Rucaparib was granted accelerated approval by the US Food and Drug Administration for the treatment of patients with BRCA1/2 mutant advanced ovarian cancer in January this year, making it the second drug in its class for this indication. It is a poly(ADPribose) polymerase inhibitor that works by blocking the repair of damaged DNA in cancer cells and triggering cell death. The approval was based on findings from 2 single-arm clinical trials in which rucaparib led to complete or partial tumor shrinkage in more than half of the patients enrolled. A pooled analysis included 106 patients from the phase 2 trials, Study 10 (NCT01482715; N = 42) and ARIEL2 (NCT01891344; N = 64), in which patients with BRCA1/2 mutation-positive ovarian cancer who had progressed on 2 or more previous chemotherapy regimens, received 600 mg rucaparib twice daily. Study 10 included only patients with platinum-sensitive disease and eligible patients were aged 18 years or older, with a known deleterious BRCA mutation, evidence of measurable disease as defined by Response Evaluation Criteria in Solid Tumors (version 1.1), sufficient archival tumor tissue, histologically confirmed high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer and relapsed disease confirmed by radiologic assessment. Meanwhile, ARIEL2 had similar eligibility criteria, except that patients with platinum-sensitive, resistant, and refractory disease were included. Both studies excluded patients with active second malignancies, and for those with a history of prior cancer that had been curatively treated, no evidence of current disease was required and chemotherapy should have been completed more than 6 months or bone marrow transplant more than 2 years before the first dose of rucaparib. Patients who had previously been treated with a PARP inhibitor, with symptomatic and/or untreated central nervous system metastases, or who had been hospitalized for bowel obstruction within the previous 3 months, were also ineligible. Across the 2 trials, the median age of trial participants was 59 years, 78% were white, and all had an Eastern Cooperative Oncology Group performance status of 0 (fully active, able to carry on all pre-disease performance without restriction) or 1 (restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature). Both trials used a surrogate endpoint for approval, measuring the percentage of patients who experienced complete or partial tumor shrinkage, the overall response rate (ORR), while taking rucaparib. In Study 10, the ORR was 60%, including a complete response (CR) rate of 10% and a partial response (PR) rate of 50%, over a median duration of response (DoR) of 7.9 months, while in ARIEL2, the ORR was 50%, including a CR of 8% and a PR of 42%, over a median DoR of Rucaparib – second PARP inhibitor hits the market for ovarian cancer