Olaparib (Lynparza)

General information

Class/mechanism: PARP (poly-ADP (adenosine diphosphate)–ribose polymerase) inhibitor. PARP participates in the alternative base-excision repair pathway that helps to repair single-strand DNA breaks. PARP is involved in normal cellular homeostasis processes during DNA transcription and cell cycle regulation. By inhibiting PARP1, PARP2, and PARP3, olaparib leads to the accumulation of single-strand breaks. In patients with a concurrent BRCA1/BRCA2 mutation, in which there are also defects in homologous recombination double strand DNA repair, this inhibition of PARP enzymatic activity and formation of the PARP-DNA complex can lead to irrecoverable DNA damage and cell death.
Route: PO
Extravasation: n/a

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the package insert.

Diseases for which it is established

• gBRCAm breast cancer
• Ovarian cancer
  • BRCAm ovarian cancer
• gBRCAm pancreatic cancer
• Prostate cancer

Patient drug information

• Olaparib (Lynparza) package insert
• Olaparib (Lynparza) patient drug information (Chemocare)
• Olaparib (Lynparza) patient drug information (UpToDate)

History of changes in FDA indication

gBRCAm Breast cancer

• 1/12/2018: Granted regular approval for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), HER2-negative metastatic breast cancer who have been treated with chemotherapy either 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. (New disease entity; based on OlympiAD)
• 3/11/2022: Approved for the adjuvant treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. (Based on OlympiA)

Ovarian cancer - PARTIALLY WITHDRAWN

• 12/19/2014: Granted initial accelerated approval as monotherapy in patients with deleterious or suspected deleterious germline BRCA-mutated (as detected by an FDA-approved test) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. (Based on Study 42)
  • 8/26/2022: Indication voluntarily withdrawn by the manufacturer; awaiting FDA withdrawal notice.
• 8/17/2017: Granted regular approval for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy. (Approval expanded to maintenance after second-line therapy; based on SOLO2 and Study 19)
• 12/19/2018: Approved for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. (Approval expanded to maintenance after first-line therapy; based on SOLO1)
• 5/8/2020: Approval expanded to include its combination with bevacizumab for first-line 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 positive status defined by either a deleterious or suspected deleterious BRCA mutation, and/or genomic instability. (Approval expanded to combination maintenance after first-line therapy; based on PAOLA-1)

gBRCAm Pancreatic cancer

• 12/27/2019: Approved for the maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) metastatic pancreatic adenocarcinoma, as detected by an FDA-approved test, whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. (New disease entity; based on POLO)

Prostate cancer

• 5/19/2020: Approved for 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. (New disease entity; based on PROfound)

History of changes in EMA indication

• 12/16/2014: Initial marketing authorization as Lynparza.

gBRCAm Breast cancer

• Uncertain date: Indicated as monotherapy for the treatment of adult patients with germline BRCA1/2-mutations, who have HER2 negative locally advanced or metastatic breast cancer. Patients should have previously been treated with an anthracycline and a taxane in the (neo)adjuvant or metastatic setting unless patients were not suitable for these treatments. Patients with hormone receptor (HR)-positive breast cancer should also have progressed on or after prior endocrine therapy, or be considered unsuitable for endocrine therapy
• 12/16/2022: Indicated as monotherapy or in combination with endocrine therapy for the adjuvant treatment of adult patients with germline BRCA1/2-mutations who have HER2-negative, high risk early breast cancer previously treated with neoadjuvant or adjuvant chemotherapy.

Ovarian cancer

• Uncertain date: Indicated as monotherapy for the maintenance treatment of adult patients with advanced (FIGO stages III and IV) BRCA1/2-mutated (germline and/or somatic) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy.
• Uncertain date: Indicated as maintenance treatment of adult patients with platinum sensitive relapsed high grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum based chemotherapy.
• Uncertain date: Indicated in combination with bevacizumab for the maintenance treatment of adult patients with advanced (FIGO stages III and IV) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy in combination with bevacizumab and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either a BRCA1/2 mutation and/or genomic instability.
• 12/16/2022: Indication withdrawn as monotherapy for the maintenance treatment of adult patients with platinum sensitive relapsed BRCA mutated (germline and/or somatic) high grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete response or partial response) to platinum based chemotherapy.

Pancreatic cancer

• Uncertain date: Indicated as monotherapy for the maintenance treatment of adult patients with germline BRCA1/2-mutations who have metastatic adenocarcinoma of the pancreas and have not progressed after a minimum of 16 weeks of platinum treatment within a first-line chemotherapy regimen.

Prostate cancer

• Uncertain date: Indicated as monotherapy for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) and BRCA1/2-mutations (germline and/or somatic) who have progressed following prior therapy that included a new hormonal agent.
• 12/16/2022: Indicated in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with mCRPC in whom chemotherapy is not clinically indicated. (Based on PROpel)

Also known as

• Code names: AZD2281, AZD-2281, KU-0059436
• Brand name: Lynparza, Olanib, Olaparix