About LYNPARZA

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What is the hypothetical mode of action for LYNPARZA combination therapy?

 

PARP and AR are important for DNA repair in prostate cancer. The interaction between PARP- and AR-signalling may explain the combined effect of LYNPARZA and abiraterone.1

In pre-clinical studies, inhibition of PARP and AR by LYNPARZA and abiraterone, respectively, results in increased DNA damage and anti-prostate cancer efficacy compared with controls.2–4

Interaction between PARP- and AR-signalling may explain the combined effect of
LYNPARZA + abiraterone observed in preclinical models2,5,6

 

Diagram explaining the hypothetical mechanism of action of Lynparza
Diagram explaining the hypothetical mechanism of action of Lynparza
The mechanism for the pharmacological rationale for the efficacy of LYNPARZA in combination with abiraterone in mCRPC is hypothetical

Extrapolation of pre-clinical experimental evidence to clinical efficacy of the combination in patients cannot be made. The role of the addition of prednisone or prednisolone corticosteroid treatment to the pharmacological and genetic effects of the combination is unknown.2,5–7


Why combine LYNPARZA with abiraterone?


Why combine LYNPARZA with abiraterone?

 

LYNPARZA cannot be combined with strong CYP3A4 inducers, such as enzalutamide, due to
expected reduced exposure and hence reduced efficacy of LYNPARZA8–10
 
Illustration of a pancreas
Illustration of a pancreas

 

Hepatic cytochrome P450 enzymes CYP3A4 and CYP3A5 are predominantly responsible for the metabolic clearance of LYNPARZA*8

*Hypothesis based on experimental models

Gear illustration with a downwards arrow
Gear illustration with a downwards arrow

 

Strong CYP3A4 inducers could reduce plasma levels of LYNPARZA, potentially affecting efficacy (e.g., co-administration of a strong CYP inducer, such as rifampicin, decreases the exposure to LYNPARZA)8 

Line graph showing downward trend
Line graph showing downward trend

 

Enzalutamide is a strong CYP3A4 inducer and therefore expected to reduce exposure of LYNPARZA and hence cannot be co-administered with LYNPARZA8–10

  




Common side effects of LYNPARZA combination therapy can be effectively
managed in most patients11–19

 

Table containing LYNPARZA combination therapy common side effects
Table containing LYNPARZA combination therapy common side effects

Management of anaemia

  • Anaemia is one of the most common side effects reported in clinical studies with LYNPARZA
  • Management strategies exist to alleviate symptoms of anaemia
  • Regular blood tests help to monitor for adverse haematological reactions, including anaemia
  • Blood transfusion may be required
  • Keeping in contact with their care team can help them manage their treatment experience

  • Contact their HCP if they experience weakness, tiredness, fever, weight loss, frequent infections, bruising, bleeding easily, breathlessness or blood in urine or stool

    - In addition to low blood cell counts and a need for blood transfusions, these may be a sign of haematological toxicity or a more serious uncommon bone marrow problem (MDS or AML) which have been reported in patients treated with LYNPARZA

    - Haematological toxicity, MDS/AML and VTE are listed as special warnings in the SmPC. Please see the LYNPARZA SmPC for further details on special warnings and precautions for use

  • Immediately report any signs or symptoms of thromboembolism, such as pain or swelling in an extremity, shortness of breath, chest pain or tachycardia

 

Management of nausea and vomiting

  • Nausea and vomiting is a common side effect within 1-2 months of LYNPARZA treatment​, usually mild-moderate in severity​
  • There are available antiemetic treatment options if they are presenting with symptoms

  • Drink caffeine-free, clear fluids​
  • Try small amounts of foods that are easy to eat several times a day
  • ​Avoid fatty, fried or very ​sweet foods​
  • Take LYNPARZA with a light meal ​or snack

 

Management of fatigue and asthenia

  • Fatigue is one of the most common side effects associated with ​cancer treatment
  • ​Fatigue management is considered a routine part of cancer care; self‑monitoring tools can be helpful and should be provided, such as a ‘fatigue diary’​
  • Other factors can contribute to fatigue (e.g. sleep problems, loss of appetite/poor nutrition, and depression)

  • Report perceived grade of fatigue to their HCP​
  • Take gentle exercise (e.g., ​walking, stretching)
  • ​Take steps to improve sleep, such as having brief naps in the afternoon​
  • Adopt a well-balanced diet

LYNPARZA is the first PARP inhibitor recommended by NICE and accepted by the SMC in mCRPC, available as both monotherapy and in combination with abiraterone and prednisone or prednisolone21-24
 

NICE recommended and SMC accepted as combination therapy for the treatment of adult patients with mCRPC in whom chemotherapy is not clinically indicated21,24
 

NICE recommended and SMC accepted as monotherapy for treating hormone-relapsed mCRPC with BRCA1/2-mutations that has progressed after NHA (such as abiraterone or enzalutamide) in adults22,23
 

Please consult the SmPC for further information to minimise the risks associated with the use of the medicine before making any prescribing decisions.

LYNPARZA tablets are indicated as monotherapy for the treatment of adult patients with mCRPC and BRCA1/2-mutations (germline and/or somatic) who have progressed following prior therapy, including an NHA.11

LYNPARZA tablets are indicated in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with mCRPC in whom chemotherapy is not clinically indicated.11

 

References
 
  1. Chaudhuri AR & Nussenzweig A. Nat Rev Mol Cell Biol. 2017;18:610–621.
  2. Schiewer MJ, et al. Cancer Discov. 2012;2:1134–1149. 
  3. Polkinghorn WR, et al. Cancer Discov. 2013;3:1245–1253. 
  4. Pommier Y, et al. Sci Transl Med. 2016;8:362ps17. 
  5. Goodwin JF, et al. Cancer Discov. 2013;3:1254–1271. 
  6. Asim M, et al. Nat Commun. 2017;8:374. 
  7. Li L, et al. Sci Signal. 2017;10;eaam7479. 
  8. Dirix L, et al. Clin Ther. 2016;38:2286–2299. 
  9. Gibbons JA, et al. Clin Pharmacokinet. 2015;54:1057–1069.  
  10. Xtandi® (enzalutamide) 40 mg film coated tablets. Summary of Product Characteristics. December 2022. Available at: https://www.medicines.org.uk/emc/product/10318/smpc Accessed January 2025.
  11. LYNPARZA (olaparib). Summary of Product Characteristics. Available at: https://www.medicines.org.uk/emc/product/9204/smpc Accessed January 2025.
  12. PROpel Protocol v1.0.
  13. American Cancer Society. Low Red Blood Cell Counts (Anaemia). Available at: https://www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/low-blood-counts/anemia.html. Accessed January 2025. 
  14. American Society of Haematology. Anaemia. Available at: https://www.hematology.org/education/patients/anemia. Accessed January 2025.
  15. American Cancer Society. Managing Nausea and Vomiting at Home. Available at: https://www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/eating-problems/nausea-and-vomiting/managing.html. Accessed January 2025. 
  16. Roubaud G, et al. Eur J Cancer 2022;170:73-84
  17. Cancer Research UK. Fatigue and cancer drugs. Available at: https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/cancer-drugs/side-effects/fatigue. Accessed January 2025. 
  18. Cancer Research UK. Managing and treating cancer fatigue. Available at: https://www.cancerresearchuk.org/about-cancer/coping/physically/fatigue/managing-treating-cancer-fatigue. Accessed January 2025. 
  19. Mayo Clinic. Cancer fatigue: Why it occurs and how to cope. Available at: https://www.mayoclinic.org/diseases-conditions/cancer/in-depth/cancer-fatigue/art-20047709. Accessed January 2025. 
  20. LaFargue CJ, et al. Lancet Oncol. 2019;20:e15–28.
  21. Olaparib with abiraterone for untreated hormone relapsed metastatic prostate cancer. NICE TA951. February 2024. Available at https://www.nice.org.uk/guidance/ta951/resources/olaparib-with-abiraterone-for-untreated-hormonerelapsed-metastatic-prostate-cancer-pdf-82615723963333. Accessed January 2025.
  22. Olaparib for previously treated BRCA mutation-positive hormone-relapsed metastatic prostate cancer. May 2023. Available at: https://www.nice.org.uk/guidance/ta887/resources/olaparib-for-previously-treated-brca-mutationpositive-hormonerelapsed-metastatic-prostate-cancer-pdf-82613738657221. Accessed January 2025.
  23. Scottish Medicines Consortium. Olaparib (Lynparza). October 2021. Available at: https://www.scottishmedicines.org.uk/medicines-advice/olaparib-lynparza-full-smc2366/. Accessed January 2025. 
  24. Scottish Medicines Consortium. Olaparib (Lynparza) March 2024. Available at: https://www.scottishmedicines.org.uk/medicines-advice/olaparib-lynparza-mcrpc-full-smc2617/. Accessed January 2025.

 

Abbreviations:
 

AML=acute myeloid leukemia; AE=adverse event; AR=androgen receptor; CBC=complete blood count; CYP=cytochrome P450; HCP=healthcare professional; HRR=homologous recombination repair; HRRm=HRR mutation; MDS=myelodysplastic syndromes; mCRPC=metastatic castration-resistant prostate cancer; NHA=new hormonal agent; NICE=National Institute for Health and Care Excellence; PARP=poly (ADP-ribose) polymerase; PARPi=PARP inhibitor; SMC=Scottish Medicines Consortium; VTE=venous thromboembolic events.

January 2025 | Job code: GB-63544

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