Drug updated on 11/1/2024
| Dosage Form | Tablet (oral; 100 mg, 150 mg) |
| Drug Class | Poly (ADP-ribose) polymerase (PARP) inhibitors |
| Ongoing and Completed Studies | ClinicalTrials.gov |
Indication
- Indicated for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy
- Indicated in combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD)-positive status defined by either a deleterious or suspected deleterious BRCA mutation, and/or genomic instability
- Indicated for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy
- Indicated for the adjuvant treatment of adult patients with deleterious or suspected deleterious gBRCAm human epidermal growth factor receptor 2 (HER2)-negative high risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy
- Indicated for the treatment of adult patients with deleterious or suspected deleterious gBRCAm, HER2-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting
- Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy
- Indicated for the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen
- Indicated for the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone
- Indicated in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC).
Latest News
Summary
- This summary is based on the review of 36 systematic review(s)/meta-analysis(es). [1-36]
- In ovarian cancer, PARP (poly (ADP-ribose) polymerase) inhibitors, including olaparib, significantly improved progression-free survival (PFS) compared to placebo (HR (hazard ratio): 0.398, 95% CI (confidence interval): 0.339-0.467) and extended overall survival (OS) (HR: 0.677, 95% CI: 0.582-0.788), with enhanced benefits observed in patients with BRCA mutations and homologous recombination-deficient (HRD) status.
- In metastatic castration-resistant prostate cancer (mCRPC) with BRCA mutations, olaparib improved PFS (HR: 0.67, 95% CI: 0.46-0.96) and OS (HR: 0.84, 95% CI: 0.72-0.98) compared to other PARP inhibitors and showed additional benefits when combined with abiraterone in patients with homologous recombination repair (HRR) mutations.
- PARP inhibitors also increased chemotherapy-free interval (CFI) (HR: 0.417), time to first subsequent therapy or death (TFST) (HR: 0.441), and time to second subsequent therapy or death (TSST) (HR: 0.574) in ovarian cancer, indicating delayed disease progression and reduced need for further treatment.
- In BRCA-mutated breast cancer, olaparib improved PFS and objective response rate (ORR) compared to chemotherapy, providing an effective alternative therapy for this patient group.
- PARP inhibitors were associated with a higher incidence of treatment-emergent adverse events (TEAEs), including both mild and grade ≥3 events, with common adverse effects such as anemia, neutropenia, thrombocytopenia, fatigue, gastrointestinal issues, and hypertension.
- Olaparib had a lower rate of grade ≥3 adverse events compared to niraparib and rucaparib, while combination therapies involving olaparib, particularly with abiraterone, showed an increased risk of high-grade anemia relative to monotherapy.
- Notable safety concerns for PARP inhibitors included hematologic toxicities (anemia, neutropenia, thrombocytopenia) and non-hematologic effects (fatigue, nausea, vomiting, diarrhea, hypertension), leading to higher discontinuation rates in some combined therapies.
- BRCA-mutated and homologous recombination-deficient (HRD) populations experienced superior outcomes with PARP inhibitors, with significant improvements in progression-free survival (PFS) and overall survival (OS) across ovarian and metastatic castration-resistant prostate cancer (mCRPC) groups. Olaparib showed marked efficacy in BRCA1/2-positive mCRPC patients, while age did not significantly affect the effectiveness of PARP inhibitors in ovarian cancer.
Product Monograph / Prescribing Information
| Document Title | Year | Source |
|---|---|---|
| Lynparza (olaparib) Prescribing Information. | 2023 | AstraZeneca Pharmaceuticals, Wilmington, DE |
Systematic Reviews / Meta-Analyses
Clinical Practice Guidelines
| Document Title | Year | Source |
|---|---|---|
| Endocrine Treatment and Targeted Therapy for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: ASCO Guideline Update | 2021 | Journal of Clinical Oncology |
| An Ontario Health (Cancer Care Ontario) clinical practice guideline: consolidation or maintenance systemic therapy for newly diagnosed stage II, III, or IV epithelial ovary, fallopian tube, or primary peritoneal carcinoma. | 2021 | Current Oncology |
| Advanced/metastatic prostate cancer. | 2021 | Alberta Health Services |
| eUpdate - newly diagnosed epithelial ovarian carcinoma treatment recommendations, clinical practice guideline | 2021 | European Society for medical Oncology |
| PARP Inhibitors in the Management of Ovarian Cancer: ASCO Guideline | 2020 | Journal of Clinical Oncology |