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This section of the website is for UK healthcare professionals only. If you are not a healthcare professional, please click here.

About LYNPARZA™ (olaparib) in prostate cancer

Great Britain prescribing information
Northern Ireland prescribing information

Dare to challenge

Introducing the first licensed PARPi in BRCA1/2-mutated metastatic castration-resistant prostate cancer (mCRPC)1

Who is LYNPARZA for?

LYNPARZA (tablets) is indicated as monotherapy for the treatment of adult patients with metastatic castration-resistant prostate cancer and patients with BRCA1/2 mutations (germline and/or somatic) who have progressed following a prior new hormonal agent.1

Choose LYNPARZA for your patients with BRCA1/2 mutations who have progressed following NHA treatment1

Median rPFS
in patients with BRCA1/2 mutations

HR=0.22
(95% CI: 0.15–0.32)
LYNPARZA 9.8 months
NHA retreatment 3.0 months1

Median OS
in patients with BRCA1/2 mutations

HR=0.63
(95% CI: 0.42–0.95)
LYNPARZA 20.1 months
NHA retreatment 14.4 months1

Safety and tolerability

Generally well tolerated in patients2

80% of patients in the PROfound study remained on LYNPARZA without discontinuing due to AEs2

Consider testing for BRCA1/2 mutations

Consider testing as soon as prostate cancer metastasises

~1 in 10 patients with mCRPC have a BRCA1/2 mutation3 – these mutations are associated with aggressive disease4,5

mCRPC demands innovative treatment options6

Prostate cancer is now the most common cancer in UK men7

~40% of men diagnosed with prostate cancer develop metastatic disease, and progression to castration resistance is expected8,9

In England, >50% of patients with advanced (stage 4) prostate cancer die within 5 years*10

*Data from 2013–2017. No UK-specific survival data for mCRPC is currently available.

By focusing on BRCA1/2 mutations with LYNPARZA, targeted medicine has now arrived in mCRPC1

Biomarker-driven treatment can target tumours with specific genetic mutations11

  • Somatic and germline mutations in the BRCA1 and BRCA2 tumour suppressor genes have been reported in patients with prostate cancer12–15

A key population

~1 in 10 patients with mCRPC have a BRCA1/2 mutation3

A prognostic factor

Prostate cancer driven by BRCA1/2 mutations is associated with aggressive disease4,5,16

A predictive biomarker

BRCA1/2 mutations increase tumour sensitivity to PARPis,17 offering a novel treatment approach after an NHA1,18

More information on testing

Treatment of BRCA1/2-mutated prostate cancer with LYNPARZA is supported by data from the PROfound study1,2,18

LYNPARZA (tablets) is indicated as monotherapy for the treatment of adult patients with metastatic castration-resistant prostate cancer and BRCA1/2 gene mutations (germline and/or somatic) who have progressed following a prior new hormonal agent.1

PROfound study design18

Randomised, controlled Phase III open-label study

*Determined by prospective tissue testing – 15-gene panel.18
Patients retreated with a different NHA; physician’s choice of either enzalutamide (160 mg QD) or abiraterone (1000 mg QD) + prednisone (5 mg BID).18
Disease progression was defined as objective imaging-based disease progression, assessed by blinded central review by an independent third-party vendor.18
§12 other mutations: BRIP1, BARD1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D and RAD54L.18

**rPFS according to RECIST 1.1 and PCWG3 by BICR.
††Key secondary endpoints were included in hierarchal testing for statistical significance. Other secondary endpoints were explored, including OS in Cohort A + B.18
‡‡ORR in evaluable patients with measurable disease at baseline, according to RECIST 1.1 by BICR.18
§§Reduction of ≥50% in the concentration of prostate-specific antigen (PSA).
***Percentage of patients with decrease in circulating tumour cell numbers from ≥5 cells per 7.5 ml of whole blood at baseline to <5 cells per 7.5 ml after baseline).18

AE = Adverse Event; BICR = Blinded Independent Central Review; BID = Twice Daily; HR = Hazard Ratio; mCRPC = Metastatic Castration-Resistant Prostate Cancer; NHA = New Hormonal Agent; ORR = Objective Response Rate; PSA = Prostate-Specific Antigen; PSA50 = Reduction of ≥50% in PSA Concentration; OS = Overall Survival; PARPi = Poly (ADP-Ribose) Polymerase Inhibitor; PCWG3 = Prostate Cancer Working Group 3; QD = Once Daily; rPFS = Radiographic Progression-Free Survival; RECIST = Response Evaluation Criteria in Solid Tumours.

Patient baseline characteristics in PROfound study – patients with BRCA1/2 mutations*1
HRR mutations screened for PROfound

PROfound study – efficacy data1

Primary endpoint: rPFS in patients with BRCA1/2 and ATM mutations (Cohort A)

  • Median rPFS was 7.4 months with LYNPARZA and 3.6 months with NHA retreatment (HR=0.34, 95% CI: 0.25–0.47, p<0.001)18

rPFS by BICR in patients with BRCA1/2 mutations1*†§

Adapted from LYNPARZA® Summary of Product Characteristics1

No conclusions can be drawn as this is an exploratory analysis.

66% of patients (86/131) who received NHA retreatment crossed over to receive LYNPARZA.2‡
This analysis is not adjusted for the crossover.

Data cut-off: 4 June 2019.
*The HR and CI were calculated using a Cox proportional hazards model that contained terms for treatment, factor and treatment by factor interaction.
Not controlled for multiplicity.
§rPFS 71% maturity.
99 patients had disease progression and had the intention to cross over. 83 patients did so in accordance with the protocol and 3 further patients received LYNPARZA outside of the trial, as they did not fulfil the eligibility criteria to cross over.2
BICR = Blinded Independent Central Review; CI = Confidence Interval; HR = Hazard Ratio; NHA = New Hormonal Agent; rPFS = Radiographic Progression-Free Survival.

OS in patients with BRCA1/2 mutations1*

Adapted from LYNPARZA® Summary of Product Characteristics1

No conclusions can be drawn as this is an exploratory analysis.

66% of patients (86/131) who received NHA retreatment crossed over to receive LYNPARZA.
This analysis is not adjusted for the crossover.

Data cut-off: 20 March 2020.
*The HR and CI were calculated using a Cox proportional hazards model that contained terms for treatment, factor and treatment by factor interaction.
Not controlled for multiplicity.
§99 patients had disease progression and had the intention to cross over. 83 patients did so in accordance with the protocol and 3 further patients received LYNPARZA outside of the trial, as they did not fulfil the eligibility criteria to cross over.2
CI = Confidence Interval; HR = Hazard Ratio; NHA = New Hormonal Agent; OS = Overall Survival.

ORR in patients with BRCA1/2 mutations1*

Adapted from LYNPARZA® Summary of Product Characteristics1

No conclusions can be drawn as this is an exploratory analysis.

66% of patients (86/131) who received NHA retreatment crossed over to receive LYNPARZA.
This analysis is not adjusted for the crossover.

Data cut-off: 4 June 2020.
*ORR in evaluable patients with measurable disease at baseline, according to RECIST1.1 by BICR. Not controlled for multiplicity.1
Odds ratios (95% CI) were not calculable.1
§99 patients had disease progression and had the intention to cross over. 83 patients did so in accordance with the protocol and 3 further patients received LYNPARZA outside of the trial, as they did not fulfil the eligibility criteria to cross over.2
BICR = Blinded Independent Central Review; CI = Confidence Interval; NHA = New Hormonal Agent; ORR = Objective Response Rate; RECIST = Response Evaluation Criteria in Solid Tumours.

LYNPARZA posology and method of administration1

LYNPARZA offers convenient oral dosing1

LYNPARZA 150 mg and 100 mg tablets

Tablets not to scale.

  • The recommended dose of LYNPARZA tablets is 300 mg, taken as two 150 mg tablets, twice daily, for a total daily dose of 600 mg1
  • Patients may take their doses with or without food, however, treatment should not be taken with grapefruit juice1
  • Treatment should be continued until disease progression or unacceptable toxicity. Medical castration with a luteinising hormone releasing hormone analogue should be continued during treatment in patients who are not surgically castrated1

LYNPARZA offers flexibility if a dose reduction is required

Dose reductions
More information on testing

References

  1. LYNPARZA (tablets) Summary of Product Characteristics.
  2. Hussain M et al. Survival with olaparib in metastatic castration-resistant prostate cancer. N Engl J Med 2020. doi: 10.1056/NEJMoa2022485 [Epub ahead of print].
  3. de Bono J et al. Central, prospective detection of homologous recombination repair gene alterations in tumour tissue from >4000 men with metastatic castration-resistant prostate cancer screened for the PROfound study. Poster 847PD. Presented at ESMO Annual Meeting, 27 September–1 October 2019, Barcelona, Spain.
  4. Castro E et al. Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer. J Clin Oncol 2013;31:1748–1757.
  5. Castro E et al. Effect of BRCA mutations on metastatic relapse and cause-specific survival after radical treatment for localised prostate cancer. Eur Urol 2015;68:186–193.
  6. Nickols GN et al. MEK-ERK signaling is a therapeutic target in metastatic castration resistant prostate cancer. Prostate Cancer Prostatic Dis 2019;22:531–538.
  7. Prostate Cancer UK. About prostate cancer. https://prostatecanceruk.org/prostate-information/about-prostate-cancer.
  8. Beltran H et al. New therapies for castration-resistant prostate cancer: efficacy and safety. Eur Urol 2011;60:279–290.
  9. Sciarra A and Salciccia S. A novel therapeutic option for castration-resistant prostate cancer: after or before chemotherapy? Eur Urol 2014;65:905–906.
  10. Office for National Statistics, Cancer survival by stage at diagnosis for England, 2019. https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/datasets/cancersurvivalratescancersurvivalinenglandadultsdiagnosed.
  11. Bailey AM, Mao Y, Zeng J et al. Implementation of biomarker-driven cancer therapy: existing tools and remaining gaps. Discov Med 2014;17:101–114.
  12. Nombela P et al. BRCA2 and other DDR genes in prostate cancer. Cancers (Basel) 2019;11:352.
  13. Abida W et al. Prospective genomic profiling of prostate cancer across disease states reveals germline and somatic alterations that may affect clinical decision making. JCO Precis Oncol 2017;2017:PO.17.00029.
  14. Dhawan M, Ryan CJ, Ashworth A. DNA Repair Deficiency Is Common in Advanced Prostate Cancer: New Therapeutic Opportunities. Oncologist 2016;21:940–945.
  15. Mateo J et al. DNA-repair defects and olaparib in metastatic prostate cancer. N Engl J Med 2015;373:1697–1708.
  16. Na R et al. Germline mutations in ATM and BRCA1/2 distinguish risk for lethal and indolent prostate cancer and are associated with early age at death. Eur Urol 2017;71:740–747.
  17. Farmer H et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 2005;434:917–921.
  18. de Bono J et al. Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med 2020;382:2091–2102 (and supplementary data).
  19. Roy R, Chun J, Powell SN. BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nat Rev Cancer 2011;12:68–78.

Supporting documentation

100 mg and 150 mg film coated tablets – Great Britain
Prescribing Information | Summary of Product Characteristics | Patient Information Leaflet

100 mg and 150 mg film coated tablets – Northern Ireland
Prescribing Information | Summary of Product Characteristics | Patient Information Leaflet

GB-27137 | Date of Preparation: March 2021