PARP Inhibitors for Ovarian Cancer: Who Qualifies, How Olaparib and Niraparib Differ, and What Maintenance Therapy Means

Research-informed explainer — last updated April 12, 2026

PARP inhibitors — a class of oral targeted drugs including olaparib, niraparib, and rucaparib — have become standard maintenance therapy after platinum-based chemotherapy for ovarian cancer, extending progression-free survival by years in the patients most likely to benefit. Eligibility is determined primarily by BRCA mutation status and a related genomic test called homologous recombination deficiency (HRD) score — not by chemotherapy response alone.

The clinical evidence for PARP inhibitors spans multiple pivotal trials conducted by researchers at leading centers. Ursula Matulonis, Professor of Medicine at Harvard Medical School and Chief of Gynecologic Oncology at Dana-Farber Cancer Institute, is one of the few investigators to have published landmark trials across three different PARP inhibitors: the NOVA niraparib maintenance trial (2,417 citations), the proof-of-concept olaparib study in BRCA-mutated recurrent ovarian cancer (2,279 citations), and the olaparib maintenance Study 19 (1,875 citations). Carol Aghajanian, Chief of Gynecologic Medical Oncology at Memorial Sloan Kettering, contributed to the SOLO-1 trial establishing olaparib maintenance in newly diagnosed BRCA-mutated ovarian cancer (2,760 citations) and the ARIEL3 rucaparib maintenance trial (1,678 citations). Deborah Armstrong, Professor of Oncology at Johns Hopkins, is the first author of the SOLO-2 olaparib maintenance trial in BRCA-mutant relapsed ovarian cancer (1,843 citations). Melinda Telli, Director of the Breast Cancer Program at Stanford Cancer Institute, published the HRD score validation study (1,128 citations) that helped establish the genomic test now used to identify PARP inhibitor benefit beyond BRCA status.

What PARP inhibitors do and why BRCA matters

PARP (poly ADP-ribose polymerase) is an enzyme that repairs single-strand breaks in DNA. When PARP is inhibited, single-strand breaks accumulate and become double-strand breaks — ordinarily a more serious type of DNA damage. Normal cells survive this because they have a backup repair mechanism called homologous recombination (HR).

Tumor cells in patients with BRCA1 or BRCA2 mutations already lack functional HR. When these cells are treated with a PARP inhibitor, they cannot repair either pathway and die — a concept called "synthetic lethality." This is why BRCA mutation status strongly predicts PARP inhibitor benefit.

Testing: BRCA and beyond

Germline BRCA testing detects inherited mutations in BRCA1 or BRCA2 that are present in every cell of the body. This test has implications for the patient's relatives and is typically performed on a blood or saliva sample.

Somatic BRCA testing detects mutations that arose only in the tumor, not in normal tissue. This is performed on tumor tissue and identifies additional patients who may benefit from PARP inhibitors.

HRD testing goes further — it identifies tumors that behave as if BRCA-mutated even when no BRCA mutation is present, due to other defects in the HR pathway. Melinda Telli's validation work showed that a genomic HRD score (measuring loss of heterozygosity and other chromosomal instability markers) predicts platinum sensitivity and PARP inhibitor benefit in patients who are BRCA-wildtype. The NOVA trial used this HRD score to identify a subset of BRCA-wildtype patients who still benefited from niraparib maintenance.

Practical implication: BRCA-negative patients are not automatically excluded from PARP inhibitors. Your oncologist should discuss whether HRD testing has been performed on your tumor.

How olaparib, niraparib, and rucaparib compare

All three approved PARP inhibitors are oral tablets or capsules taken daily. They share a mechanism but differ in label indications, approved biomarker subgroups, and side effect profiles.

Olaparib — the first FDA-approved PARP inhibitor in ovarian cancer — showed in Study 19 (a phase II trial, Matulonis) that maintenance therapy after platinum-sensitive relapse doubled progression-free survival (8.4 vs 4.8 months) versus placebo, with the greatest benefit in BRCA-mutated patients. SOLO-2 (Armstrong) confirmed these results in a phase III BRCA-selected population.

Niraparib — the NOVA trial (Matulonis as senior author) enrolled both BRCA-mutated and non-mutated patients. In the BRCA cohort, niraparib extended median progression-free survival from 5.5 months to 21 months. In the non-BRCA HRD-positive cohort, from 3.8 months to 12.9 months. Niraparib does not require any biomarker selection under the current PRIMA-based first-line label, though benefit is largest in BRCA-mutated and HRD-positive patients.

Key side effect differences: Niraparib has a higher rate of thrombocytopenia (low platelets) than olaparib and requires careful dose individualization based on baseline weight and platelet count. Olaparib's most common side effects are nausea and fatigue. Both drugs carry a small risk of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with prolonged use — estimated at 1–1.5% over 2 years.

What maintenance therapy means in practice

"Maintenance therapy" means starting a drug after achieving response to chemotherapy — not at first recurrence or progression. The goal is to extend the period of remission, not to treat active disease. Most trials enrolled patients within 8 weeks of completing platinum-based chemotherapy.

Duration of maintenance therapy typically continues until disease progression or unacceptable toxicity. In SOLO-1, maintenance olaparib continued for up to 2 years in newly diagnosed BRCA-mutated patients; updated analyses showed persistent overall survival benefit at 5 years.

Questions to ask your doctor

• Has my tumor been tested for BRCA mutations — both germline and somatic? Has HRD testing been performed?
• Based on my test results, which PARP inhibitor is most appropriate, and does my BRCA or HRD status affect which drug offers me the most benefit?
• When should maintenance therapy start — how soon after I complete chemotherapy?
• What side effects should I monitor, and are there dose adjustments I should know about?
• If my BRCA test was negative, does a normal HRD score mean PARP inhibitors are not appropriate for me?

The bottom line

PARP inhibitors are now a standard component of ovarian cancer treatment for patients whose tumors carry BRCA mutations or show HRD, and niraparib may benefit some patients regardless of biomarker status. The key to accessing the right drug is getting the right tests — germline BRCA, somatic BRCA, and HRD — at the time of diagnosis or relapse. Patients who have not been tested should ask their oncologist to revisit this question before accepting a treatment plan that does not include a PARP inhibitor discussion.