The FDA has approved rucaparib (Rubraca, Clovis Oncology, Inc.) for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. The agency granted regular approval for rucaparib in this second, broader, and earlier-line indication on a priority-review timeline based on positive data from a phase 3 trial. Biomarker testing is not required for patients to be prescribed rucaparib in this maintenance treatment indication.
In addition to granting rucaparib approval in this second indication, the FDA converted the approval of the initial treatment indication from accelerated to regular approval.
In December 2017, the FDA accepted the rucaparib supplemental new drug application and granted priority review status. The rucaparib maintenance treatment approval is based on positive results from the phase 3 ARIEL3 study, which evaluated rucaparib in the ovarian cancer maintenance treatment setting among three populations: 1) BRCA-mutant (BRCAmut+), 2) homologous recombination deficiency-positive inclusive of BRCAmut+, and 3) all patients treated in ARIEL3. The study enrolled a total of 564 patients.
ARIEL3 successfully achieved both its primary and key secondary endpoints: extending investigator-assessed progression-free survival versus placebo in all patients treated, regardless of BRCA status.
The most common adverse reactions (greater than or equal to 20% of patients; Common Terminology Criteria for Adverse Events [CTCAE] grade 1–4) were nausea, fatigue/asthenia, abdominal pain/distention, rash, dysgeusia, anemia, aspartate transaminase (AST) and alanine transaminase (ALT) elevation, constipation, vomiting, diarrhea, thrombocytopenia, nasopharyngitis/upper respiratory tract infection, stomatitis, decreased appetite, and neutropenia. The most common laboratory abnormalities (greater than or equal to 25% of patients; CTCAE grade 1–4) were increase in creatinine, decrease in hemoglobin, increase in cholesterol, increase in ALT, increase in increase in AST, decrease in platelets, decrease in leukocytes, decrease in neutrophils, increase in alkaline phosphatase, and decrease in lymphocytes. The majority of adverse reactions and laboratory abnormalities were grade 1–2.
Rucaparib is an oral, small-molecule inhibitor of poly (ADP-ribose) polymerase 1 (PARP1), PARP2, and PARP3 being developed in ovarian cancer as well as several additional solid tumor indications. Studies open for enrollment or under consideration include ovarian, prostate, breast, gastroesophageal, pancreatic, lung, and bladder cancers.
Rucaparib is FDA-approved for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. It is also approved for the treatment of adult patients with deleterious BRCA mutation (germline and/or somatic)-associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies, and selected for therapy based on an FDA-approved companion diagnostic for rucaparib.
Source: Clovis Oncology; April 6, 2018.