Niraparib Approved: A Treatment Prolonging Survival in Stage 4 or Recurrent Ovarian Cancer

On 27 March 2017, the FDA approved niraparib (trade name Zejula®) for maintenance treatment of adults with recurrent ovarian, fallopian tube or primary peritoneal cancer whose tumors had previously shrunk completely or partially (complete or partial response) with platinum-based chemotherapy but whose disease subsequently recurred.

Niraparib blocks the PARP pathway, preventing cancer cells from repairing their DNA and thereby slowing or stopping tumor growth

Niraparib inhibits poly ADP-ribose polymerase (PARP), an enzyme involved in repairing damaged DNA. A detailed mechanism of action is provided at the end of this article.

The safety and efficacy of niraparib were evaluated in a study involving 553 patients with recurrent epidermal ovarian, fallopian tube or primary peritoneal cancer who had received platinum-based chemotherapy at least twice and had a complete or partial response to their latest platinum-based treatment, a clinical trial . Patients were tested using an FDA-approved test to determine whether they had the specific BRCA gene mutation known as a germline mutation . The duration without cancer growth after treatment (progression-free survival) was measured in patients with and without germline BRCA mutations. Among patients with a BRCA mutation, average progression-free survival was 21 months in the niraparib arm and 5,5 months in the placebo arm. Among those without a germline BRCA mutation, average progression-free survival was 9,3 months with niraparib and 3,9 with placebo (treatment without active ingredients). Thus, niraparib significantly prolonged survival in patients both with and without BRCA mutations. However, its benefit was more pronounced in those with BRCA mutations.

Niraparib side effects include low red blood cell (anemia), platelet (thrombocytopenia) and white blood cell (neutropenia or leukopenia) counts, palpitations, nausea, constipation , vomiting, abdominal pain / bloating, mouth sores (mucositis), diarrhea, indigestion (dyspepsia), dry mouth, fatigue , reduced appetite, urinary tract infection, liver problems (elevated AST / ALT), muscle pain (myalgia), back pain, joint pain (arthralgia), headache, dizziness, unusual taste, insomnia, anxiety, cold-like symptoms (nasopharyngitis), shortness of breath, cough, rash and high blood pressure (hypertension).

Because cancer cells divide much more frequently and rapidly than normal cells, more DNA damage, or mutations, occurs. When DNA damage occurs, various intracellular mechanisms either repair it or, if it is beyond repair, cause the cell to undergo apoptosis. Both PARP and BRCA play roles in DNA repair. When the PARP inhibitor niraparib is used in ovarian cancer, the cancer cell partially loses its ability to repair DNA. If these cells also have a BRCA mutation, their ability to repair DNA and remain immortal is reduced much further.