CALQUENCE®▼ (acalabrutinib)
CALQUENCE® (acalabrutinib) is een remmer van het Bruton Tyrosine Kinase (BTK)
voor de behandeling van chronische lymfatische leukemie (CLL).1
Klinische studies
In onderstaande paragrafen worden de belangrijkste resultaten van de klinische studies die de werkzaamheid en veiligheid van acalabrutinib in CLL onderzochten toegelicht.
In september 2021 organiseerde AstraZeneca het live event ‘Ask the expert: All about acalabrutinib’. Tijdens dit event werden de belangrijkste klinische gegevens van acalabrutinib gepresenteerd door Prof Janssens (UZ Leuven) en werden patiëntencasussen besproken door Prof Pagel (Swedish Cancer Institute in Seattle, US). Deze presentaties werden gevolgd door een live Q&A over het gebruik van acalabrutinib in de klinische praktijk.
In februari 2022 heeft AstraZeneca in samenwerking met de Société Luxembourgeoise d’Oncologie opnieuw een expertmeeting georganiseerd. Dit keer werd de presentatie van de klinische data en van enkele patiëntencasussen gegeven door Prof Brown (Dana-Farber Cancer Institute, Boston, US). Ook deze meeting werd afgesloten met een interessante live Q&A.
ELEVATE-TN : Een pivotale Fase III studie van CALQUENCE® ± obinutuzumab in therapienaïeve CLL patiënten5,6
79% risk reduction in disease progression or death with CALQUENCE vs GClb after 5 years of follow-up4-7
aHazard ratio based on Cox-Proportional-Hazards model stratified by 17p deletion status (yes vs no based on interactive voice/web response system). bP-value based on log-rank test stratified by 17p deletion status (yes vs no based on interactive voice/web response system).
Consistent PFS improvement across patient subgroups in favour of CALQUENCE® vs GCIb
Investigator-assessed PFS in patients with Del(17p) and/or Mutated TP53
aHazard ratio was based on unstratified Cox-Proportional-Hazards model. bP-value was based on unstratified log-rank test.
Investigator-assessed PFS in patients with (A) Unmutated and (B) Mutated IGHV
IGHVum (A)
aHazard ratio was based on unstratified Cox-Proportional-Hazards model; bP-value was based on unstratified log-rank test.
IGHVm (B)
aHazard ratio was based on unstratified Cox-Proportional-Hazards model; bP-value was based on unstratified log-rank test.
Most common adverse events were Grade 1 or 2
Common adverse events (≥15%, all grades) with CALQUENCE® ± G7
Data are n (%) unless otherwise specified..
Klik hier om uw AstraZeneca hospitaalverantwoordelijke hematologie te contacteren indien u graag een geprinte of digitale versie van de ELEVATE-TN publicatie zou wensen te ontvangen.
AstraZeneca heeft in samenwerking met Dr Patel (Swedish Cancer Institute, Seattle) en Ariez ook een podcast opgenomen waarin Dr Patel de langetermijn data van acalabrutinib in CLL, die gepresenteerd werden tijdens het 2022 EHA congres, bespreekt.
ELEVATE-RR : De non-inferioriteit, Fase III studie van CALQUENCE® vs ibrutinib in de hervallen/refractaire setting8,9
CALQUENCE® met its primary endpoint of PFS non-inferiority in head-to-head trial vs ibrutinib
Median IRC-assessed PFS was 38.4 months in both arms at a median follow-up of 40.9 months
Secondary endpoint: Atrial fibrillation/flutter events of any grade were significantly lower with CALQUENCE® vs ibrutinib
*Difference in any grade incidence rates: -6.6% (95% CI -12.2 to -0.9), P=0.02. Data are n (%) unless otherwise specified among patients with events of afib/flutter. Risk factors for atrial fibrillation/flutter were based on medical review and included hypertension, diabetes mellitus, myocardial infarction/ischemia and cardiac disease.
In a study by Shanafelt et al, 6.1% of CLL patients had a prior history of atrial fibrillation at diagnosis, with an annual incidence of 1%.10
Lower cumulative incidences of any grade atrial fibrillation/flutter, hypertension, bleeding events, diarrhea and arthralgia with CALQUENCE® vs ibrutinib
Atrial fibrillation/flutter
Hypertension
Bleeding events
Diarrhea
Arthralgia
CALQUENCE® demonstrated clear safety differences vs ibrutinib
Note: Data are reported as No. (%). Adverse events are reported as individual MedDRA preferred terms. Higher incidentes are shown in bold text for terms with statistical differences. Abbreviation: MedDRA, Medical Dictionary for Regulatory Activities. a Descriptive two-sided P,.05 on the basis of Barnard's exact test without multiplicity adjustment for all-grade adverse events. b Descriptive two-sided P , .05 on the basis of Barnard's exact test without multiplicity adjustment for grade 3 or higher adverse events.
Discontinuation due to adverse events was lower with CALQUENCE® than with ibrutinib
Median duration of exposure: CALQUENCE®, 38.3 months; ibrutinib, 35.5 months
Klik hier om uw AstraZeneca hospitaalverantwoordelijke hematologie te contacteren indien u graag een geprinte of digitale versie van de ELEVATE-RR publicatie zou wensen te ontvangen.
AstraZeneca heeft in samenwerking met Prof O’Brien (California-Irvine) en Ariez (uitgever van The Belgian Journal of Hematology) een podcast opgenomen waarin Prof O’Brien de waarde van acalabrutinib in CLL toelicht in het licht van de resultaten van de ELEVATE-RR studie.
ASCEND : Een pivotale, Fase III studie van CALQUENCE® in patiënten met hervallen/refractaire CLL11
71% reduction in risk of progression with CALQUENCE® vs IdR/BR
INV-assessed PFS after a median follow-up of 36 months
CALQUENCE® vs ldR/BR
aPFS rates were based on the IWCLL 2008 criteria in patients with R/R CLL. Patients were censored at the time when any subsequent anticancer therapies were received. bHazard ratio was based on stratified Cox proportional-hazards model, stratified by randomization stratification factors as recorded in an interactive voice/web response system. cP-value was based on stratified log-rank test, stratified by randomization stratification factors as recorded in an interactive voice/web response system. dHazard ratios were based on unstratified Cox-Proportional-Hazards model. eP-values were based on unstratified log-rank test.
CALQUENCE® vs ldR vs BR
aPFS rates were based on the IWCLL 2008 criteria in patients with R/R CLL. Patients were censored at the time when any subsequent anticancer therapies were received. bHazard ratio was based on stratified Cox proportional-hazards model, stratified by randomization stratification factors as recorded in an interactive voice/web response system. cP-value was based on stratified log-rank test, stratified by randomization stratification factors as recorded in an interactive voice/web response system. dHazard ratios were based on unstratified Cox-Proportional-Hazards model. eP-values were based on unstratified log-rank test.
PFS benefit with CALQUENCE® independent of High-Risk Features
PFS by del(17p)
Note: PFS rates were based on the IWCLL 2008 criteria in patients with R/R CLL. Patients were censored at the time when any subsequent anticancer therapies were received.
aBecause there were no IdR/BR-treated patients at risk by 42 mo in the del(17p) subgroup, 42-mo PFS rates were not available for that analysis. bHazard ratio was based on stratified Cox proportional-hazards model, stratified by randomization stratification factors as recorded in an interactive voice/web response system. cP-value was based on stratified log-rank test, stratified by randomization stratification factors as recorded in an interactive voice/web response system. dHazard ratios were based on unstratified Cox-Proportional-Hazards model. eP-values were based on unstratified log-rank test.
PFS by lGHV
Note: PFS rates were based on the IWCLL 2008 criteria in patients with R/R CLL. Patients were censored at the time when any subsequent anticancer therapies were received.
aBecause there were no IdR/BR-treated patients at risk by 42 mo in the del(17p) subgroup, 42-mo PFS rates were not available for that analysis. bHazard ratio was based on stratified Cox proportional-hazards model, stratified by randomization stratification factors as recorded in an interactive voice/web response system. cP-value was based on stratified log-rank test, stratified by randomization stratification factors as recorded in an interactive voice/web response system. dHazard ratios were based on unstratified Cox-Proportional-Hazards model. eP-values were based on unstratified log-rank test.
Klik hier om uw AstraZeneca hospitaalverantwoordelijke hematologie te contacteren indien u graag een geprinte of digitale versie van de ASCEND publicatie zou wensen te ontvangen.
AstraZeneca heeft in samenwerking met Dr Patel (Swedish Cancer Institute, Seattle) en Ariez ook een podcast opgenomen waarin Dr Patel de langetermijn data van acalabrutinib in CLL, die gepresenteerd werden tijdens het 2022 EHA congres, bespreekt.