PURPOSE Acalabrutinib, a highly selective, potent, Bruton tyrosine kinase inhibitor, was evaluated in this global, multicenter, randomized, open-label, phase III study in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). METHODS Eligible patients, aged $ 18 years with R/R CLL, were randomly assigned 1:1 centrally and stratified by del(17p) status, Eastern Cooperative Oncology Group performance status score, and number of prior lines of therapy. Patients received acalabrutinib monotherapy or investigator’s choice (idelalisib plus rituximab [I-R] or bendamustine plus rituximab [B-R]). The primary end point was progression-free survival (PFS) assessed by an independent review committee (IRC) in the intent-to-treat population. Key secondary end points included IRC-assessed overall response rate, overall survival, and safety. RESULTS From February 21, 2017, to January 17, 2018, a total of 398 patients were assessed for eligibility; 310 patients were randomly assigned to acalabrutinib monotherapy (n 5 155) or investigator’s choice (n 5 155; I-R, n 5 119; B-R, n 5 36). Patients had received a median of two prior therapies (range, 1-10). After a median follow-up of 16.1 months (range, 0.03-22.4 months), median PFS was significantly longer with acalabrutinib monotherapy (PFS not reached) compared with investigator’s choice (16.5 months [95% CI, 14.0 to 17.1 months]; hazard ratio, 0.31 [95% CI, 0.20 to 0.49]; P, .0001). Estimated 12-month PFS was 88% (95% CI, 81% to 92%) for acalabrutinib and 68% (95% CI, 59% to 75%) for investigator’s choice. Serious adverse events occurred in 29% of patients (n 5 44 of 154) treated with acalabrutinib monotherapy, 56% (n 5 66 of 118) with I-R, and 26% (n 5 9 of 35) with B-R. Deaths occurred in 10% (n 5 15 of 154), 11% (n 5 13 of 118), and 14% (n 5 5 of 35) of patients receiving acalabrutinib monotherapy, I-R, and B-R, respectively. CONCLUSION Acalabrutinib significantly improved PFS compared with I-R or B-R and has an acceptable safety profile in patients with R/R CLL.
Ascend: Phase III, randomized trial of acalabrutinib versus idelalisib plus rituximab or bendamustine plus rituximab in relapsed or refractory chronic lymphocytic leukemia
Ghia P.
;
2020-01-01
Abstract
PURPOSE Acalabrutinib, a highly selective, potent, Bruton tyrosine kinase inhibitor, was evaluated in this global, multicenter, randomized, open-label, phase III study in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). METHODS Eligible patients, aged $ 18 years with R/R CLL, were randomly assigned 1:1 centrally and stratified by del(17p) status, Eastern Cooperative Oncology Group performance status score, and number of prior lines of therapy. Patients received acalabrutinib monotherapy or investigator’s choice (idelalisib plus rituximab [I-R] or bendamustine plus rituximab [B-R]). The primary end point was progression-free survival (PFS) assessed by an independent review committee (IRC) in the intent-to-treat population. Key secondary end points included IRC-assessed overall response rate, overall survival, and safety. RESULTS From February 21, 2017, to January 17, 2018, a total of 398 patients were assessed for eligibility; 310 patients were randomly assigned to acalabrutinib monotherapy (n 5 155) or investigator’s choice (n 5 155; I-R, n 5 119; B-R, n 5 36). Patients had received a median of two prior therapies (range, 1-10). After a median follow-up of 16.1 months (range, 0.03-22.4 months), median PFS was significantly longer with acalabrutinib monotherapy (PFS not reached) compared with investigator’s choice (16.5 months [95% CI, 14.0 to 17.1 months]; hazard ratio, 0.31 [95% CI, 0.20 to 0.49]; P, .0001). Estimated 12-month PFS was 88% (95% CI, 81% to 92%) for acalabrutinib and 68% (95% CI, 59% to 75%) for investigator’s choice. Serious adverse events occurred in 29% of patients (n 5 44 of 154) treated with acalabrutinib monotherapy, 56% (n 5 66 of 118) with I-R, and 26% (n 5 9 of 35) with B-R. Deaths occurred in 10% (n 5 15 of 154), 11% (n 5 13 of 118), and 14% (n 5 5 of 35) of patients receiving acalabrutinib monotherapy, I-R, and B-R, respectively. CONCLUSION Acalabrutinib significantly improved PFS compared with I-R or B-R and has an acceptable safety profile in patients with R/R CLL.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
