Rubraca Approved as Maintenance Treatment for Patients with Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

May 2018, Vol 8, No 5 - FDA Approvals, News & Updates


On April 6, 2018, rucaparib (Rubraca; Clovis Oncology), a poly (ADP-ribose) polymerase (PARP) inhibitor, received a new indication by the FDA for the maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who achieved complete or partial response with platinum-based chemotherapy.

On the same day, the FDA also approved the FoundationFocus CDxBRCA LOH, a next-generation sequencing assay, for the identifi­cation of homologous recombination deficiency (HRD) status in tumor samples. HRD is a new somatic mutation found in less than 10% of ovarian cancers.

Rucaparib was initially approved in December 2016 for the treatment of women with advanced ovarian cancer who had received ≥2 chemotherapies and whose tumors are associated with the deleterious BRCA genetic mutation, as identified by the first next-­generation sequencing test approved by the FDA, the FoundationFocus CDx BRCA companion diagnostic.

The FoundationFocus CDx BRCA LOH represents a new version of this next-generation sequencing test, which was approved by the FDA in association with the new indication for rucaparib for the detection of the HRD mutation in women with ovarian cancer.

The FDA approved this new indication based on results from ARIEL3, a randomized, double-blind, placebo-controlled study with 561 patients who had recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer. Patients had received ≥2 cycles of platinum-based chemotherapy and achieved complete or partial response with the most recent cycle.

The next-generation sequencing assay was used on tumor tissue samples to determine the presence of a deleterious somatic or germline BRCA mutation (tBRCA), and the percentage of genomic loss of heterozygosity (LOH). Patients with HRD were defined as tBRCA-positive and/or LOH high.

The median progression-free survival in all patients was 10.8 months with rucaparib versus 5.4 months with placebo; 13.6 versus 5.4 months, respectively, in the HRD subgroup; and 16.6 versus 5.4 months, respectively, in the tBRCA subgroup.

The most common (≥20%) adverse reactions reported with rucap­arib include nausea, fatigue, asthenia, abdominal pain or distension, rash, dysgeusia, anemia, elevated alanine transaminase and aspartate transaminase levels, constipation, vomiting, diarrhea, thrombocytopenia, nasopharyngitis, upper respiratory infection, stomatitis, decreased appetite, and neutropenia.

A total of 15% of patients receiving rucaparib and 2% of those receiving placebo discontinued treatment because of adverse events.