| Drug Name |
Olaparib |
| Drug ID |
BADD_D01601 |
| Description |
Olaparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1, PARP2, and PARP3. PARP enzymes are involved in normal cellular homeostasis, such as DNA transcription, cell cycle regulation, and DNA repair. Olaparib has been shown to inhibit growth of select tumor cell lines in vitro and decrease tumor growth in mouse xenograft models of human cancer both as monotherapy or following platinum-based chemotherapy. Increased cytotoxicity and anti-tumor activity following treatment with olaparib were noted in cell lines and mouse tumor models with deficiencies in BRCA. In vitro studies have shown that olaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complex, resulting in disruption of cellular homeostasis and cell death.
Olaparib is available as oral tablets marketed under the brand name Lynparza and was initially indicated as a maintenance therapy or monotherapy for the treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer. On January 12, 2018, FDA expanded the approved use of Lynparza to include chemotherapy-experienced patients with germline breast cancer susceptibility gene (BRCA) mutated, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. In a randomized clinical trial involving patients with HER2-negative metastatic breast cancer with a germline BRCA mutation, the median progression-free survival for patients taking Lynparza was 7 months compared to 4.2 months for patients taking chemotherapy only. Patient selection for this newly-approved indication can be performed based on an FDA-approved genetic test, called the BRACAnalysis CDx.
Moreover, in December of 2018 the FDA further approved the categorization and use of Lynparza (olaparib) as frontline maintenance therapy in ovarian cancer, making the medication the first time a PARP inhibitor has been approved in the first-line maintenance setting [L5086]. This new approval for frontline maintenance now allows patients who have had surgery and complete or partial response to platinum-based therapy after being first diagnosed with the cancer to be treated with olaparib to decrease the risk of recurrence or delay it significantly [L5086]. This approval is based on findings from the phase 3 SOLO-1 trial for olaparib, which demonstrated the capacity for the agent to reduce the risk of disease progression or death by 70% in patients with BRCA-mutant advanced ovarian cancer who were in complete or partial response to platinum-based chemotherapy [L5086]. It is expected that the ability to offer this important first-line maintenance treatment option to eligible patients may slow down or even stop the natural course of disease progression [L5086]. |
| Indications and Usage |
Olaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for the treatment of:
- Ovarian cancer, in which the medication is intended for [a] the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy, or [b] for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy [FDA Label]. Select patients for therapy based on an FDA-approved companion diagnostic for olaparib [FDA Label].
- Breast cancer, in which the medication is intended for use in patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have previously 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 treatment [FDA Label]. Select patients for therapy based on an FDA-approved companion diagnostic for olaparib [FDA Label]. |
| Marketing Status |
approved |
| ATC Code |
L01XK01 |
| DrugBank ID |
DB09074
|
| KEGG ID |
D09730
|
| MeSH ID |
C531550
|
| PubChem ID |
23725625
|
| TTD Drug ID |
D0J9HW
|
| NDC Product Code |
17228-0668; 17228-0679; 71796-034; 0074-0668; 0074-0679; 54893-0099; 0310-0668; 46708-904; 49187-0740; 49187-0741; 54864-843; 65129-1464; 0310-0679; 65129-1400; 68554-0120 |
| UNII |
WOH1JD9AR8
|
| Synonyms |
olaparib | AZD 2281 | AZD2281 | AZD-2281 | AZD221 | Lynparza |
