Rucaparib Receives FDA Approval for Ovarian, Fallopian Tube and Peritoneal Cancer Treatment

For maintenance (continued) treatment of recurrent ovarian, fallopian tube or primary peritoneal cancer, the poly ADP-ribose polymerase (PARP) inhibitor rucaparib (brand name Rubraca) received FDAapproval on 6 April 2018. Patients receiving rucaparib must previously have had a complete or partial response to platinum -based chemotherapy.

The approval is based on results in 561 patients with recurrent ovarian, fallopian tube or primary peritoneal cancer who had previously received at least two platinum-based chemotherapy treatments and had a complete or partial response, in the ARIEL3 clinical study. Randomized in a 2:1 ratio, 372 received oral rucaparib twice daily at 600 mg, while 189 received placebo . Treatment continued until disease progression or unacceptable toxicity (side effects).

How Does Rucaparib Work?

The PARP enzyme is an important DNA repair mechanism. Drugs suppressing PARP aim to prevent cancer cells from repairing their own DNA and therefore proliferating. However, cells have more than one DNA repair system. BRCA genes govern another important system. Some breast, ovarian and prostate cancers have BRCA mutations inherited from parents (germline) or acquired during life (somatic). Giving a PARP-suppressing drug to BRCA mutation-positive patients can produce highly effective treatment outcomes.

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In ARIEL3, next-generation sequencing (NGS) of tumor tissue can identify BRCA gene hereditary or somatic mutations. Loss of heterozygosity in BRCA can also be detected. Determining its percentage indicates how active BRCA is. Homologous recombination deficiency (HDR) is defined as BRCA positivity or high BRCA heterozygosity. PARP inhibitors are expected to work in patients with BRCA mutations. BRCA gene testing is recommended when planning these medicines.

ARIEL3 Results Can Be Summarized as Follows:

• For all patients, progression-free survival (the time disease is kept under control with treatment) was 10.8 months with rucaparib versus 5.4 months with placebo,
• In the somatic BRCA mutation subgroup called HRD, progression-free survival was 13.6 versus 5.4 months,
• In the hereditary/germline BRCA mutation subgroup called tBRCA, progression-free survival was 16.6 versus 5.4 months.
• Rucaparib reduced disease progression risk by % 64 – 77.

The FDA also approved FoundationFocusTM CDx BRCA LOH, a complementary genetic diagnostic test on tumor samples to determine HRD status.

In ARIEL3, the most common side effects in at least % 20 of rucaparib recipients were, nausea, fatigue (including asthenia), abdominal pain / distension, rash, dysgeusia, anemia, elevated ALT / AST, constipation, vomiting, diarrhea, thrombocytopenia (low clotting cell count), nasopharyngitis (upper respiratory tract infection), stomatitis, decreased appetite and neutropenia. Myelodysplastic syndrome and / or acute myeloid leukemia occurred among rucaparib recipients in 372 patients, 7 (% 1.9), and among placebo recipients in 189 patients, 1 (% 0,5). Discontinuation because of side effects occurred in % 15 of rucaparib recipients and % 2 of placebo recipients.

The recommended rucaparib doseis 600 mg orally twice daily, with or without food (two 300 mg tablets).

Previously, in 2017, the other two PARP inhibitors, olaparib and niraparib had received approval for the same diseases under the same conditions.