Paolo Ghia, MD, Ph.D. of Università Vita-Salute San Raffaele speaks about ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia
Intent —
In this national, multicenter, randomized, open-label phase III review, acalabrutinib, a highly selective, active Bruton tyrosine kinase inhibitor, was evaluated in patients with relapsed / refractory (R / R) chronic lymphocytic leukemia ( CLL).
METHODS
Qualified patients, aged 18 years with R / R CLL, were randomly allocated 1:1 centrally and stratified by del(17p) status, success status score of the Eastern Cooperative Oncology Group, and a number of prior therapy lines. Acalabrutinib monotherapy or investigator option (idelalisib plus rituximab [I-R] or bendamustine plus rituximab [B-R]) was administered to patients. The primary endpoint was progression-free survival (PFS), evaluated in the intent-to – treat population by an independent review committee (IRC). The IRC-assessed overall response time, overall survival, and protection were main secondary endpoints.
OUTCOMES
A total of 398 patients were evaluated for eligibility from February 21, 2017 to January 17, 2018; 310 patients were randomly allocated to acalabrutinib monotherapy (n = 155) or the investigator’s preference (n = 155; I-R, n = 119; B-R, n = 36). A median of two prior therapies (range, 1-10) were obtained by patients. Median PFS was slightly longer with acalabrutinib monotherapy (PFS not achieved) after a median follow-up of 16.1 months (range, 0.03-22.4 months) compared with the investigator’s option (16.5 months [95 percent CI, 14.0 to 17.1 months]; hazard ratio, 0.31 [95 percent CI, 0.20 to 0.49]; P < .0001). The median 12-month PFS for acalabrutinib was 88 percent (95 percent CI, 81 percent to 92 percent) and 68 percent (95 percent CI, 59 percent to 75 percent) for the option of the investigator. In 29 percent of patients (n = 44 of 154) treated with acalabrutinib monotherapy, 56 percent (n = 66 of 118) with I-R, and 26 percent (n = 9 of 35) with B-R, severe adverse effects occurred. Deaths occurred in 10% (n = 15 of 154), 11% (n = 13 of 118), and 14% (n = 5 of 35) of patients who received monotherapy with acalabrutinib, I-R, and B-R, respectively.Â
CONCLUSION Â
Compared with I-R or B-R, acalabrutinib substantially improved PFS and has a reasonable safety profile in R / R CLL patients.