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.Olaparib (Lynparza) package insertOlaparib (Lynparza) package insert (locally hosted backup)Lynparza manufacturer's website
Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, Mortimer P, Swaisland H, Lau A, O'Connor MJ, Ashworth A, Carmichael J, Kaye SB, Schellens JH, de Bono JS. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009 Jul 9;361(2):123-34. Epub 2009 Jun 24. link to original article EuroPMC
Route: PO
Extravasation: n/a
*IUPHAR/BPS
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, or the package insert.
==Diseases for which it is established==
*gBRCAm breast cancer
*Ovarian cancer
**BRCAm ovarian cancer
*gBRCAm pancreatic cancer
*Prostate cancer
==Diseases for which it is used==
*Endometrial cancer
==Patient drug information==
*Olaparib (Lynparza) package insert
*Olaparib (Lynparza) patient drug information (Chemocare)Olaparib (Lynparza) patient drug information (Chemocare)
*Olaparib (Lynparza) patient drug information (UpToDate)Olaparib (Lynparza)patient drug information (UpToDate)
==History of changes in FDA indication==
===gBRCAm Breast cancer===
*2018-01-12: 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)
*2022-03-11: 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===
*2014-12-19: 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)
**2022-08-26: Accelerated approval voluntarily withdrawn by the manufacturer; awaiting FDA withdrawal notice. 
*2017-08-17: 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)
*2018-12-19: 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)
*2020-05-08: 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===
*2019-12-27: 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===
*2020-05-19: 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)
*2023-05-31: Approved with abiraterone and prednisone (or prednisolone) for adult patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC), as determined by an FDA-approved companion diagnostic test. (Based on PROpel)
==History of changes in EMA indication==
===gBRCAm Breast cancer===
*2019-04-08: 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
*2022-08-02: Indicated as monotherapy 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.
*2022-08-02: Indicated 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===
*2014-12-16: Initial marketing authorization as Lynparza. Lynparza is indicated as monotherapy for the 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. (Based on Study 19)
*2019-06-12: 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.
*2020-03-11: 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.
*2022-12-16: 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===
*2020-07-03: 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. (Based on POLO)
===Prostate cancer===
*2020-03-11: 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.
*2022-12-16: 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)
==History of changes in Health Canada indication==
*2016-04-29: Initial notice of compliance with conditions
*2018-05-02: Conditions were met
*2018-05-04: Notice of compliance with conditions as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed (PSR) BRCA wild type high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy.
*2022-07-27: Notice of compliance with conditions 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.
==History of changes in PMDA indication==
===Breast cancer===
*2018-01-19: New approval for the maintenance treatment of recurrent ovarian cancer in patients who are in a complete or partial response to platinum-based chemotherapy.
*2018-07-02: New additional indication for the treatment of unresectable or recurrent BRCA mutation-positive and HER2-negative breast cancer in patients who have previously been treated with chemotherapy.
*2022-08-24: New indication and a new dosage for the postoperative adjuvant treatment of BRCA mutation-positive and HER2-negative breast cancer with a high risk of recurrence.
===Ovarian cancer===
*2019-06-18: New indication for maintenance treatment of BRCA mutation-positive ovarian cancer in patients who have received first chemotherapy.
*2020-12-25: New indication and new dosage for the maintenance treatment of homologous recombination deficiency (HRD)-positive ovarian cancer in patients who have received first chemotherapy including treatment with bevacizumab.
===Pancreatic cancer===
*2020-12-25: new indication and a new dosage for maintenance therapy of unresectable BRCA mutation-positive pancreatic cancer after chemotherapy including treatment with platinum-based antineoplastic drugs.
===Prostate cancer===
*2020-12-25: New indication and new dosage for the treatment of metastatic, BRCA mutation-positive, castration-resistant prostate cancer.
==Also known as==
*Code names: AZD-2281, KU-0059436
*Brand name: Bdparp, Bracanat, Canrib, Ibyra, Lynparza, Lynza, Obrenza, Olabuzz, Olarigen, Olaparix, Olanib, Ribaxa, Riparib
==References==
Category:Drugs
Category:Oral medications
Category:Protein expression-specific medications
Category:Mutation-specific medications
Category:PARP1 inhibitors
Category:PARP2 inhibitors
Category:Breast cancer medications
Category:Endometrial cancer medications
Category:Ovarian cancer medications
Category:Pancreatic cancer medications
Category:Prostate cancer medications
Category:EMA approved in 2014
Category:FDA approved in 2014
Category:Health Canada approved in 2016
Category:PMDA approved in 2018
Category:AstraZeneca product