In onderstaande paragrafen worden de belangrijkste resultaten van de klinische studies die de werkzaamheid en veiligheid van acalabrutinib in CLL onderzochten toegelicht.

79% risk reduction in disease progression or death with CALQUENCE vs GClb after 5 years of follow-up^4-7

^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.. 

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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

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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.

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