Drug updated on 9/4/2024
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
- Lynparza (olaparib) is used for the maintenance treatment of adult patients with BRCA-mutated advanced ovarian, fallopian tube, or peritoneal cancer, as well as in combination with bevacizumab for HRD-positive ovarian cancers. It is also indicated for BRCA-mutated HER2-negative breast cancer, both early-stage and metastatic, and for maintenance in BRCA-mutated metastatic pancreatic adenocarcinoma. Additionally, Lynparza is used for the treatment of metastatic castration-resistant prostate cancer with BRCA or homologous recombination repair gene mutations.
- This summary is based on the review of 21 systematic review(s)/meta-analysis(es). [1-21]
- PARP inhibitors, including olaparib, significantly improved progression-free survival (PFS) in recurrent ovarian cancer across subgroups: total population HR 0.34, BRCA mutant HR 0.24, germline BRCA mutant HR 0.23, BRCA wild-type HR 0.50. Olaparib extended PFS compared to controls (HR 0.49).
- No statistically significant differences were observed in overall survival (OS) or objective response rate (ORR) between olaparib and control groups.
- Combination of PARP inhibitors with androgen receptor signaling inhibitors (ARSI) significantly improved radiographic PFS in metastatic castration-resistant prostate cancer (mCRPC) (HR 0.62); olaparib combined with abiraterone also showed prolonged rPFS (RR 0.66). PARPi + ARSI combination reduced the risk of death by 16% (HR 0.84); no significant OS difference with olaparib and abiraterone (HR 0.87).
- PARP inhibitors demonstrated high-certainty improvement in PFS (HR 0.63) and a small OS advantage (HR 0.87) in locally advanced/metastatic HER2-negative, BRCA germline mutated breast cancer. Moderate improvement in tumor response rate was noted compared to other treatments (66.9% vs. 48.9%).
- Olaparib significantly improved Triple-Negative Breast Cancer (TNBC) PFS (HR 0.43) and objective response rate (ORR 2.57) compared to chemotherapy.
- In ovarian cancer, PARP inhibitors, including olaparib, increased the risk of severe adverse events (AEs), particularly grade ≥ 3 AEs, which were manageable with dose modification.
- In prostate cancer, the combination of olaparib and abiraterone was associated with an increased incidence of high-grade anemia, and hematological toxicities such as anemia, neutropenia, and thrombocytopenia were common with PARP inhibitor treatments.
- In breast cancer, a high occurrence of grade 3 or higher adverse events was observed (59.4% vs. 64.5% in the non-PARP arm), with hematological events such as anemia, neutropenia, and thrombocytopenia being significantly higher in the PARP inhibitors group.
- The reviewed studies provide specific population and subgroup information, particularly highlighting significant improvements in progression-free survival (PFS) in subgroups with BRCA mutations across ovarian, prostate, and breast cancers, with clinically relevant findings including effective outcomes in both BRCA-mutant and wild-type ovarian cancer populations, metastatic castration-resistant prostate cancer (mCRPC) in BRCA1/2 mutation subgroups, and HER2-negative, BRCA germline mutated breast cancer, including triple-negative breast cancer (TNBC) with BRCA mutations.
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 |
---|---|---|
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 |
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 |
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 |