Lynparza™ (olaparib)
LYNPARZA® is geïndiceerd voor 4 therapeutische indicaties. Klik op de icoontjes voor meer informatie.
Borstkanker
Over Lynparza
Werkingsmechanisme
Olaparib is een sterke remmer van menselijke poly (ADP-ribose) polymerase-enzymen (PARP-1, PARP-2 en PARP-3) en het is aangetoond dat dit middel de groei van bepaalde tumorcellijnen in vitro en de groei van tumoren in vivo remt, ofwel als opzichzelfstaande behandeling of in combinatie met gevestigde chemotherapieën.1 Klik hier om de video te downloaden.
Samenvattend: BRCAm tumoren hebben een unieke moleculaire biologie die hen gevoelig maakt voor PARP-remming.3,4
Lynparza® remt PARP op twee manieren:*3-5
- Door de enzymatische activiteit te remmen3-5
- Door de vorming van gevangen PARP-DNA complexen te verhogen3-5
In vitro activity does not always correlate with clinical efficacy.
*The exact mechanism of action of LYNPARZA® remains a subject of research.
PARP=poly (ADP-ribose) polymerase; PARPi=poly (ADP-ribose) polymerase inhibitor.
Samenvatting van de resultaten
De OlympiAD-studie was een gerandomiseerde, open-label fase III-studie waarin olaparib monotherapie werd vergeleken met standaard chemotherapie bij patiënten met een gBRCA-mutatie en menselijke epidermale groeifactorreceptor type 2 (HER2)-negatieve gemetastaseerde borstkanker die niet meer dan twee eerdere chemotherapieën voor gemetastaseerde ziekte hadden gekregen.6
In OlympiAD, verbeterde Lynparza® resultaten vs. chemotherapie6,7
Medians shown of LYNPARZA® vs. chemotherapy (treatment of physician's choice – eribulin, capecitabine or vinorelbine).
*TTR was assessed in patients with measurable disease who had a response to treatment – 100/167 LYNPARZA® patients and 19/66 chemotherapy patients.
†PFS2 assesses the time from treatment initiation to the second disease progression or death from any cause.‡>1.5 years OS at 64% data maturity (trial not powered for OS; data not mature at cut-o ).
CI=confidence interval; HR=hazard ratio;'OS=overall survival; PFS=progression-free survival; PFS2=progression-free survival 2 (time to second progression); TTR=time to response.
Medians shown of LYNPARZA® vs. chemotherapy (treatment of physician's choice – eribulin, capecitabine or vinorelbine).
*TTR was assessed in patients with measurable disease who had a response to treatment – 100/167 LYNPARZA® patients and 19/66 chemotherapy patients.
†PFS2 assesses the time from treatment initiation to the second disease progression or death from any cause.‡>1.5 years OS at 64% data maturity (trial not powered for OS; data not mature at cut-o ).
CI=confidence interval; HR=hazard ratio;'OS=overall survival; PFS=progression-free survival; PFS2=progression-free survival 2 (time to second progression); TTR=time to response.
Lynparza® verbetert de PFS in vergelijking met chemotherapie.6 Lynparza® bereikte een PFS van 7 maanden, en kan de noodzaak van chemotherapie uitstellen.6
PFS in gBRCAm HER2-negative mBC patients6
CI=confidence interval; gBRCAm=germline BRCA-mutated; HR=hazard ratio; mBC=metastatic breast cancer; PFS=progression-free survival.
Het gebruik van Lynparza® in eerste lijn suggereerde een groter voordeel voor de OS dan het gebruik in de volgende lijnen.7 Bij 64% data maturiteit bereikten patiënten behandeld met LYNPARZA® een mediane OS van 19,3 maanden versus 17,1 met chemotherapie (HR=0,90; 95% CI: 0,66-1,23; P=0,513).7
OS in gBRCAm HER2-negative first-line mBC patients*7
OlympiAD was not powered to detect a difference in OS between treatment arms; there was no statistically significant difference in OS between treatment arms.
*'First-line mBC patients' refers to patients who received no prior chemotherapy in the metastatic setting.
CI=confidence interval; gBRCAm=germline BRCA-mutated; HR=hazard ratio; laBC=locally advanced breast cancer; mBC=metastatic breast cancer; NS=not signifcant; OS=overall survival.
OS in gBRCAm HER2-negative second- and third-line mBC patients†7
OlympiAD was not powered to detect a difference in OS between treatment arms; there was no statistically signifcant difference in OS between treatment arms.
†'Second- and third-line mBC patients' refers to patients who received prior chemotherapy in the metastatic setting.
‡gBRCAm HER2-negative patients with locally advanced or metastatic breast cancer are eligible for first-line LYNPARZA® if they have previously been treated with an anthracycline and a taxane in the neoadjuvant or adjuvant setting, unless they were not suitable for these treatments. Patients with hormone receptor-positive breast cancer should also have progressed on or after prior endocrine therapy, or be considered unsuitable for endocrine therapy.
CI=confidence interval; gBRCAm=germline BRCA-mutated; HR=hazard ratio; laBC=locally advanced breast cancer; mBC=metastatic breast cancer; NS=not signi cant; OS=overall survival.
Lynparza® verbeterde de levenskwaliteit (quality of life, QoL) in vergelijking met chemotherapie.*6,8 Lynparza® patiënten hadden een 3,9-punts verbetering in QoL ten opzichte van de uitgangswaarde vs. een 3,6-punts daling ten opzichte van de uitgangswaarde met chemotherapie, wat een statistisch significante 7,5-punts verbetering in verandering van QoL vanaf uitgangswaarde vergeleken met chemotherapie.*†8
Lynparza® significantly delayed time to deterioration of QoL vs. chemotherapy8
Median TTD findings should be interpreted with caution as PRO data were collected only until disease progression; most patients had not reached the 10-point threshold criterion for deterioration at this time.
*Assessed with the EORTC QLQ-C30, which was completed by patients at baseline and then every 6 weeks until disease progression. It comprises of 30 questions about global health/QoL, functional health and symptoms.
†Treatment of physician’s choice (eribulin, capecitabine or vinorelbine).
CI=confidence interval; EORTC QLQ-C30=European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; gBRCAm=germline BRCA-mutated; HR=hazard ratio; PRO=patient-reported outcomes; QoL=quality of life; TTD=time to deterioration.
Veiligheidsprofiel
De bijwerkingen in OlympiAD waren meestal mild tot matig van ernst en beheersbaar door onderbreking of vermindering van de dosis.8
Adverse events reported in ≥15% of patients in OlympiAD*8
Alopecia trad op bij 3,4 % van de patiënten in de Lynparza-arm, in vergelijking met 13,2 % in de chemotherapie-arm.7
*Includes AEs of any grade that occurred in at least 15% of patients in either group and grade 3 AEs, which were graded according to the NCI CTCAE, version 4.0.
†The neutropenia category included febrile neutropenia, granulocytopenia, decreased granulocyte count, neutropenia, neutropenic sepsis, decreased neutrophil count and neutropenic infection.
‡The anaemia category included anaemia, decreased haemoglobin level, decreased hematocrit, decreased red-cell count and erythropenia.
§205 patients were assigned to receive LYNPARZA® and all 205 received treatment and were included in safety analyses.
¶97 patients were assigned to receive standard therapy, 6 did not receive treatment owing to patient decision. 91 received treatment and were included in the safety analyses.
AE=adverse event; gBRCAm=germline BRCA-mutated; NCI CTCAE=National Cancer Institute Common Terminology Criteria of Adverse Events.
Onderzoek naar genetische mutaties
Aanbevelingen voor het testen van BRCA1/2 in borstkanker:
| ESMO | Vroegtijdige BRCA-tests bij patiënten met gevorderde borstkanker.9 |
Klik hier voor de terugbetaling van genetische testen in België.
Vroegtijdig testen om de behandeling te optimaliseren:
TNBC=triple-negative breast cancer; gBRCA=germline BRCA; laBC=locally advanced breast cancer; mBC=metastatic breast cancer