FDA-Approved PARP Inhibitors for Ovarian Cancer
Three PARP inhibitors are currently FDA-approved for ovarian cancer: olaparib, niraparib, and rucaparib, with specific indications varying by treatment setting, BRCA mutation status, and line of therapy. 1
First-Line Maintenance Therapy (Newly Diagnosed Advanced Disease)
The following PARP inhibitors are approved for maintenance after response to platinum-based chemotherapy in newly diagnosed advanced ovarian cancer:
Olaparib 300 mg twice daily: Approved for patients with germline or somatic BRCA1/2 mutations 1
Niraparib 200-300 mg once daily: Approved for patients with germline BRCA mutations AND for BRCA wild-type patients 1, 2
Olaparib plus bevacizumab: Approved for patients with homologous recombination deficiency (HRD-positive), regardless of BRCA status 1, 2
Clinical Pearl: The frontline setting is where patients derive the greatest benefit from PARP inhibitors, particularly those with BRCA mutations, making this the preferred timing for PARP inhibitor initiation. 1
Second-Line or Later Maintenance Therapy (Recurrent Platinum-Sensitive Disease)
Following FDA requests in recent years due to concerns about overall survival in wild-type BRCA patients, second-line maintenance indications have been significantly restricted to BRCA-mutated patients only: 1
Olaparib 300 mg twice daily: Limited to germline or somatic BRCA mutations 1
Niraparib 200-300 mg once daily: Limited to germline BRCA mutations only (more restrictive than first-line) 1
Rucaparib 600 mg twice daily: Limited to germline or somatic BRCA mutations 1
Critical Restriction: PARP inhibitors should only be used in recurrent maintenance if patients have not previously received a PARP inhibitor (Category 1) OR if disease did not progress during prior PARP inhibitor treatment (Category 2A). 1
Treatment Setting (Recurrent Disease After ≥2-3 Prior Lines)
Important Update: Most treatment indications for recurrent disease have been voluntarily withdrawn due to lack of overall survival benefit and potential harm in platinum-resistant disease. 1
Rucaparib was voluntarily withdrawn in June 2022 for treating BRCA-mutated ovarian cancer after ≥2 prior chemotherapy lines due to no demonstrated OS benefit and worse outcomes in platinum-resistant disease. 1
Olaparib retains limited approval for treatment of germline BRCA-mutated ovarian cancer after ≥3 prior lines of chemotherapy, though this indication is rarely used given superior outcomes with earlier PARP inhibitor initiation. 1
Key Clinical Considerations
Biomarker Testing Requirements
All patients with newly diagnosed advanced ovarian cancer should undergo germline and somatic BRCA1/2 testing, plus HRD testing if BRCA wild-type, to determine eligibility for PARP inhibitor maintenance therapy. 3, 4
Histology Restrictions
These approvals and recommendations specifically apply to high-grade serous or grade 2/3 endometrioid ovarian cancer. Evidence is lacking for other histologic subtypes (clear cell, mucinous, low-grade serous, carcinosarcoma). 1
Combination Therapy Caution
Bevacizumab plus PARP inhibitor combination is NOT recommended as a maintenance option in the recurrent disease setting, only in the frontline setting for HRD-positive tumors. 1
Veliparib Status
Veliparib is mentioned in ASCO guidelines but is not commercially available and should not be substituted with other PARP inhibitors due to different safety profiles and dosing requirements. 1
Common Pitfalls to Avoid
Do not use PARP inhibitors as second-line maintenance in BRCA wild-type patients - this practice was common before 2024 but FDA indications were restricted due to lack of OS benefit and potential harm. 1
Do not substitute one PARP inhibitor for another in combination regimens without established safety data for that specific combination. 1
Do not delay PARP inhibitor initiation to later lines - the greatest benefit occurs when used as first-line maintenance in BRCA-mutated patients. 1