Lynparza™ (olaparib)

LYNPARZA® est indiqué dans 4 indications thérapeutiques. 

Lynpara (olaparib) est le premier inhibiteur de PARP (Poly-ADP-Ribose-Polymérase), qui permet aux femmes atteintes d'un cancer de l’ovaire récidivant sensible au platine avec une mutation BRCA (BReast CAncer) de prolonger la survie sans progression1-3 

Cancer de la prostate

À propos de Lynparza

Mécanisme d’action

L’olaparib est un puissant inhibiteur des enzymes poly (ADP-ribose) polymérase humaines (PARP-1, PARP-2 et PARP-3) et il a été montré qu'il inhibait la croissance de certaines lignées de cellules tumorales in vitro et la croissance tumorale in vivo soit en monothérapie soit en association avec des chimiothérapies de référence.1

Pour résumer: Les tumeurs BRCAm ont une biologie moléculaire unique qui les rend sensibles à l'inhibition de la PARP.3,4

Lynparza® inhibe la PARP de deux façons:*3-5

  • En inhibant l’activité enzymatique3-4
  • En augmentant la formation de complexes PARP-ADN piégés3-4

*Healthy cells may also be affected by Lynparza®.†Based on preclinical data. The exact mechanism of action of Lynparza® remains the subject of research.BRCAm = breast cancer gene mutation; PARP = poly ADP-ribose polymerase inhibitor; ADP = adenosine diphospate; HRR = homologous recombination repair.

Résumé des résultats

*Determined by prospective tumour tissue testing – 15-gene panel.5
†Three patients in the LYNPARZA® arm in Cohort A had co-occurring mutations in both BRCA and ATM.7
‡Patients retreated with a different NHA; physician’s choice of either enzalutamide (160 mg QD) or abiraterone (1000 mg QD) + prednisone (5 mg BID).5
rPFS according to RECIST 1.1 & PCWG3 by BICR. ORR in evaluable patients with measurable disease at baseline, according to RECIST 1.1 by BICR.5
 §Key secondary endpoints were included in hierarchical testing for statistical significance.5,8
ATM = ataxia-telangiectasia mutated; BICR=blinded independent central review; BID=twice daily; BRCA = Breast cancer gene; HR­R=homologous recombination repair; mCRPC=metastatic castration-resistant prostate cancer ; NHA=new hormonal agent; ORR=ob­jective response rate; OS=overall survival; PARPi=poly (ADP-ribose) polymerase inhibitor; PCWG3=Prostate cancer Working Group 3; QD=once daily; RECIST=Response Evaluation Criteria in Solid Tumors; rPFS=radiographic progression-free survival.

Survie globale chez les patients mutés BRCA1,5

Data presented for 160 BRCA-mutated patients. 141 had single mutations in BRCA1 or BRCA2; 19 had BRCA1/2 and co-occurring mutations in other HRR genes.9
*The HR and CI were calculated using a Cox proportional hazards model that contains terms for treatment, factor and treatment by factor interaction.1
BRCA=breast cancer gene; BRCA1=breast cancer gene 1; BRCA2=breast cancer gene 2; CI=confidence interval; HR=hazard ratio; NHA=new hormonal agent; OS=overall survival; n=number

Survie radiographique sans progression chez les patients mutés BRCA1,5

Data presented for 160 BRCA-mutated patients. 141 had single mutations in BRCA1 or BRCA2; 19 had BRCA1/2 and co-occurring mutations in other HRR genes.9
*The HR and CI were calculated using a Cox proportional hazards model that contains terms for treatment, factor and treatment by factor interaction. rPFS 71% maturity at data cut off.1
BRCA = BReast CAncer gene; BRCA1 = BReast CAncer gene 1; BRCA2 = BReast CAncer gene 2; CI = confidence interval; HR = hazard ratio; NHA = new hormonal agent; ORR = objective response rate; rPFS = radiographic progression-free survival.

Profil de sécurité

Le profil de sécurité observé dans l'étude PROfound5,10 était conforme au profil de sécurité général de Lynparza®1

Effets secondaires rapportés chez ≥10% des patients dans PROfound1,5,10

Pulmonary embolism occurred in 5% of patients with LYNPARZA vs. 1% with NHA retreatment, none were fatal.10
Safety data from PROfound is presented for the overall population, including BRCA1/2, ATM and 12 other HRR mutations. LYNPARZA® should only be prescribed in the appropriate indicated population.1,10
*Includes anaemia, decreased haemoglobin level, decreased red cell count, decreased haematocrit level, erythropaenia, macrocytic anaemia, normochromic anaemia, normochromic normocytic anaemia, and normocytic anaemia. Anaemia was reported in 49% of the patients, and a decreased haemoglobin level was reported in less than 1%.10
†One patient in the control group did not receive treatment.10
AE = adverse event; ATM = ataxia-telangiectasia mutated; BRCA1=breast cancer gene 1; BRCA2=breast cancer gene 2; HRR=homologous recombination repair; NHA=new hormonal agent.

Contrôle génétique

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Tumor testing* is reimbursed for mCRPC patients

  • Germline testing is recommended in patients with a family history of cancer and should be considered in all patients with metastatic prostate cancer
  • *If BRCA mutations in tumour are found, refer to genetic counselling for confirmatory germline testing.11,12
    BRCA=breast cancer gene; BRCA1=BReast CAncer gene 1; BRCA2=breast cancer gene 2; mCRPC=metastatic castration-resistant prostate cancer; NHA=new hormonal Agent
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