FDA Approval: Niraparib (Zejula) for Ovarian Cancer

Maintenance is a different kind of treatment

Most cancer drug news is about shrinking a tumor. Niraparib, sold as Zejula, was approved in 2017 for something else: maintenance therapy. Its FDA label carries an Initial U.S. Approval date of 2017.

Maintenance therapy is given after a course of chemotherapy has already worked, with the goal of holding the disease back rather than knocking it down. The person taking it is not in crisis. They are in a response, and the drug is there to make that response last.

That distinction shapes everything about how the trial was designed and how the result should be read.

What was approved, and on what evidence

The 2017 approval covered niraparib as maintenance therapy in women who had already had a recurrence of high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer, and who had a complete or partial response to platinum-based chemotherapy. It made niraparib the third PARP inhibitor approved for ovarian cancer.

The trial randomized more than 550 patients to niraparib or placebo. All had already had at least two courses of platinum-based chemotherapy, and their cancer had responded fully or partly to the most recent one. The main endpoint was progression-free survival, meaning time lived without the disease worsening.

The trial had two groups. Among women with inherited BRCA mutations, median progression-free survival was 21 months with niraparib and 5.5 months with placebo. Among women without BRCA mutations, it was 9.3 months with niraparib and 3.9 months with placebo.

That second result was the notable one. It meant the drug worked in women whose tumors had no inherited BRCA mutation at all.

NCI notes that the FDA changed this approval in November 2022. NCI's current listing describes two maintenance uses: after first-line platinum chemotherapy in advanced disease with a complete or partial response, and in recurrent disease with a germline BRCA1 or BRCA2 mutation and a complete or partial response to platinum chemotherapy.

How a PARP inhibitor works

PARP is an enzyme that helps cells repair damaged DNA. Blocking it leaves single-strand breaks unrepaired.

Healthy cells have a backup repair system. Cancer cells with faulty BRCA genes do not, because BRCA1 and BRCA2 are part of that backup. Take away PARP and the backup at the same time, and the cell accumulates damage it cannot fix.

NCI quotes Elise Kohn of NCI's Division of Cancer Treatment and Diagnosis calling this the beginning of a new class, the DNA repair-inhibitor class, with research expanding into breast, prostate, pancreatic, and gastric cancers.

When to get checked

This is the hardest part of ovarian cancer, and it is worth stating without softening. NCI says these cancers may not cause early signs or symptoms, and that when symptoms do appear, the cancer is often advanced.

There is no recommended screening test for ovarian cancer in women at average risk.

NCI lists these signs and symptoms:

• Pain, swelling, or a feeling of pressure in the abdomen or pelvis.
• A sudden or frequent urge to urinate.
• Trouble eating, or feeling full quickly.
• A lump in the pelvic area.
• Gastrointestinal problems such as gas, bloating, or constipation.

NCI's advice is specific about timing. If these get worse or do not go away on their own, check with a doctor so any problem can be diagnosed and treated as early as possible. Persistence is the signal, not severity.

Family history matters too. Women with a family history of ovarian cancer are at increased risk, some of these cancers are caused by inherited gene mutations, and women at increased risk may consider risk-reducing surgery.

Pelvic exam, CA-125, and the stage that follows

Diagnosis and staging use the same set of tests. A pelvic exam checks the size, shape, and position of the uterus and ovaries. A CA-125 assay measures a substance released by cells into the blood, though a raised level can also come from other conditions such as endometriosis. Ultrasound, including transvaginal ultrasound, and CT scanning map the pelvis and abdomen.

Stage runs from I to IV. Stage IVA means cancer cells in fluid around the lungs. Stage IVB means spread to organs and tissues outside the abdomen, including lymph nodes in the groin.

For treatment purposes NCI groups them more simply. Stage I is treated as early cancer. Stages II, III, and IV are treated as advanced cancer.

Surgery first, then chemotherapy, then maintenance

NCI lists surgery, chemotherapy, and targeted therapy as the standard types, with radiation therapy and immunotherapy also used.

Most patients have surgery to remove as much of the tumor as possible. That can include hysterectomy, removal of the uterus, and removal of the ovaries and fallopian tubes. Platinum-based chemotherapy usually follows. Maintenance therapy, where niraparib sits, comes after that. Our page on targeted therapy covers the wider class, and biomarker testing covers the BRCA testing that shapes these decisions.

The numbers behind late diagnosis

These SEER figures describe the whole US population and predict nothing for one person.

Five-year relative survival for ovarian cancer is 52.0 percent for cases from 2016 to 2022. By stage it is 91.9 percent while confined to the ovary, 70.1 percent once it reaches nearby lymph nodes, and 31.5 percent once it has spread further. Only 22 percent are caught at that first stage, and 54 percent are already distant. An estimated 21,010 new cases and 12,450 deaths are projected for 2026, and median age at diagnosis is 63.

The gap between 91.9 and 31.5 percent, next to the fact that most cases are found late, is the shape of the problem this whole field is working on. Our page on ovarian cancer covers it further.

What this trial cannot tell you

The registration trial measured progression-free survival, not overall survival. A gap of 21 months versus 5.5 months is large, but it counts scan findings, not deaths.

Side effects matter in a maintenance setting, because the drug is taken while a person feels relatively well. NCI reported anemia, palpitations, nausea, and fatigue as common, and noted risks of myelodysplastic syndrome and acute myeloid leukemia, which are serious blood disorders.

Sources

• NCI Cancer Currents, niraparib approved as maintenance therapy for ovarian cancer — https://www.cancer.gov/news-events/cancer-currents-blog/2017/fda-niraparib-ovarian
• NCI, Niraparib Tosylate Monohydrate — https://www.cancer.gov/about-cancer/treatment/drugs/niraparibtosylatemonohydrate
• DailyMed, ZEJULA (niraparib) label, Initial U.S. Approval 2017 — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b7f675e2-159c-490c-b6f4-3f16d9492b7d
• NCI PDQ, Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal Cancer Treatment (Patient Version) — https://www.cancer.gov/types/ovarian/patient/ovarian-epithelial-treatment-pdq
• SEER Cancer Stat Facts, Ovarian Cancer — https://seer.cancer.gov/statfacts/html/ovary.html

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.

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