Compared with two rituximab-containing regimens, acalabrutinib significantly improves progression-free survival (PFS) in patients with chronic lymphocytic leukemia (CLL) and has a comparable safety profile to these regimens, according to the results of a phase III randomized trial.
Results of the trial were published in the Journal of Clinical Oncology (May 27, 2020; doi:10.1200/JCO.19.03355).
Acalabrutinib—a highly selective and potent Bruton tyrosine kinase inhibitor—was evaluated in the ASCEND trial – a global, multicenter, randomized, open-label, phase III study for patients with relapsed or refractory CLL that was led by Paolo Ghia, MD, PhD, Università Vita-Salute San Raffaele (Milano, Italy). Eligible patients (aged at least 18 years) from February 2017 to January 2018 were randomly assigned (1:1) to receive acalabrutinib monotherapy (n = 155) or investigator’s choice of either idelalisib plus rituximab (n = 119) or bendamustine plus rituximab (n = 36). All patients were stratified by del(17p) status, ECOG performance status score, and number of prior lines of therapy.
The primary endpoint of the study was PFS assessed by an independent review committee in the intention-to-treat population. Among the secondary endpoints were independent review committee-assessed overall response rate, overall survival, and safety.
Researchers noted that patients had received a median of two prior therapies.
After a median follow-up of 16.1 months, median PFS was significantly longer patients in the acalabrutinib arm (not reached) compared with investigator’s choice arms (16.5 months). The estimated 12-month PFS was 88% (95% CI, 81% to 92%) for acalabrutinib vs 68% (95% CI, 59% to 75%) for investigator’s choice therapies.
Additionally, Dr Ghia and colleagues noted that serious adverse events occurred in 29% of patients treated with acalabrutinib monotherapy compared with 56% and 26% of patients treated with idelalisib plus rituximab and bendamustine plus rituximab, respectively. Mortality occurred in 10%, 11%, and 14%, respectively.
“Acalabrutinib significantly improved PFS compared with idelalisib plus rituximab or bendamustine plus rituximab and has an acceptable safety profile in patients with relapsed or refractory CLL,” authors of the study concluded.—Zachary Bessette
