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About LYNPARZA (olaparib)

Updated on 09/08/2019

ONCOLOGY

LYNPARZA (tablets) is the ONLY PARP inhibitor (PARPi) approved as first-line maintenance therapy in newly diagnosed women with BRCAm advanced ovarian cancer2

LYNPARZA tablet indications

LYNPARZA is indicated as a 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.2

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.2

LYNPARZA is 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.2

LYNPARZA capsule indication

LYNPARZA is indicated 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 or partial) to platinum-based chemotherapy.3

LYNPARZA (tablets) (100 mg and 150 mg) should not be substituted for LYNPARZA (capsules) (50 mg) on a milligram-to-milligram basis due to differences in the dosing and bioavailability of each formulation. Therefore, the specific dose recommendations for each formulation should be followed.2

LYNPARZA (tablets) is recommended by NICE for use within the Cancer Drugs Fund as an option for the maintenance treatment of BRCAm, advanced (FIGO stages 3 and 4) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer that has responded to first-line platinum-based chemotherapy in adults.1 Find out full details of the NICE guidance.

LYNPARZA (capsules) is recommended by NICE for use within the CDF as an option for treating adults with relapsed, platinum-sensitive ovarian, fallopian tube or peritoneal cancer who have BRCA1 or BRCA2 mutations and whose disease has responded to platinum-based chemotherapy only if they have had 3 or more courses of platinum-based chemotherapy.4 Find out full details of the NICE guidance.

For more information on LYNPARZA in Ovarian Cancer please click here

Are you familiar with PARP inhibition (PARPi)?

Every day, thousands of DNA lesions occur in cells, including single-strand breaks (SSBs).5

The enzyme poly (ADP-ribose) polymerase (PARP) is a key protein required for the efficient repair of these SSBs through a mechanism known as base excision repair (BER).6

When PARP function is inhibited, cells cannot effectively repair SSBs and the unrepaired SSBs are converted to double-strand breaks (DSBs) during DNA replication, which then require repair via the homologous recombination repair pathway (HRR).5,7

Cells that are deficient in homologous recombination repair are therefore unable to repair these DSBs, ultimately resulting in cellular death.

Cells that are deficient in homologous recombination repair are therefore unable to repair these DSBs, ultimately resulting in cellular death image

BRCA mutations and PARP inhibition

BRCA1 and BRCA2 (collectively known as BRCA) are human genes that play a central role in repairing DNA DSBs via the homologous recombination pathway.8

BRCA mutations are an example of one type of mutation that can result in HRD. The presence of a BRCA mutation in a patient is therefore another marker that can be used to select patients that might be sensitive to PARP inhibition pathway.9,10

LYNPARZA selectively induces cancer cell death by inhibiting the function of PARP, in combination with the BRCA mutation (absence of functional BRCA).9

Approximately 22% of high-grade epithelial ovarian cancer patients carry a BRCA mutation which can be confirmed by genetic testing.8,11–13

22% of epithelial ovarian cancer patients carry a BRCAm  image

References

  1. NICE guidance on olaparib for maintenance treatment of ovarian, fallopian tube or peritoneal cancer that has a BRCA germline mutation after response to first-line platinum-based chemotherapy. Available from: https://www.nice.org.uk/guidance/indevelopment/gid-ta10257.
  2. LYNPARZA 100 mg and 150 mg film-coated tablets Summary of Product Characteristics.
  3. LYNPARZA 50 mg hard capsules Summary of Product Characteristics.
  4. NICE guidance on olaparib for maintenance treatment of relapsed, platinum-sensitive, BRCA mutation-positive ovarian, fallopian tube and peritoneal cancer after response to second-line or subsequent platinum-based chemotherapy. Available from: https://www.nice.org.uk/guidance/ta381
  5. Aly, A. & Ganesan, S. BRCA1, PARP, and 53BP1: conditional synthetic lethality and synthetic viability. J Mol Cell Biol 3, 66–74 (2011).
  6. Langelier, M.-F., Riccio, A. A. & Pascal, J. M. PARP-2 and PARP-3 are selectively activated by 5′ phosphorylated DNA breaks through an allosteric regulatory mechanism shared with PARP-1. Nucleic Acids Res 42, 7762–7775 (2014).
  7. Weston, V. J. et al. The PARP inhibitor olaparib induces significant killing of ATM-deficient lymphoid tumor cells in vitro and in vivo. Blood 116, 4578–4587 (2010).
  8. Pennington, K. P. et al. Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas. Clin. Cancer Res. 20, 764–775 (2014).
  9. Ledermann, J. et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. The Lancet Oncology 15, 852–861 (2014).
  10. Girolimetti, G. et al. BRCA-associated ovarian cancer: from molecular genetics to risk management. Biomed Res Int 2014, 787143 (2014).
  11. Vergote, I. et al. Current perspectives on recommendations for BRCA genetic testing in ovarian cancer patients. Eur. J. Cancer 69, 127–134 (2016).
  12. Moschetta, M., George, A., Kaye, S. B. & Banerjee, S. BRCA somatic mutations and epigenetic BRCA modifications in serous ovarian cancer. Ann. Oncol. 27, 1449–1455 (2016).
  13. Pal, T. et al. BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. Cancer 104, 2807–2816 (2005).

Supporting documentation

100 mg and 150 mg film coated (tablets)
Prescribing Information | Summary of Product Characteristics | Patient Information Leaflet

50 mg hard capsules
Prescribing Information | Summary of Product Characteristics | Patient Information Leaflet

GB-17803 | Date of Preparation: August 2019