Paolo Ghia1,2, Andrzej Pluta3, Malgorzata Wach4, Daniel Lysak5, Tomas Kozak6, Martin Simkovic7, Polina Kaplan8, Iryna Kraychok9, Arpad Illes10, Javier de la Serna11, Sean Dolan12, Phillip Campbell13, Gerardo Musuraca14, Abraham Jacob15, Eric Avery16, Jae Hoon Lee17, Wei Liang18, Priti Patel18, Cheng Quah18, Wojciech Jurczak19. 1. Università Vita-Salute San Raffaele, Milano, Italy. 2. Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele, Milano, Italy. 3. Szpital Specjalistyczny w Brzozowie im. Ks. Markiewicza, Oddział Hematologii Onkologicznej z Klinicznym Oddziałem Przeszczepiania Szpiku, Brzozow, Poland. 4. Department of Hemato-Oncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland. 5. Fakultní Nemocnice Plzeň, Pilsen, Czech Republic. 6. Fakultní Nemocnice Královske Vinohrady, Prague, Czech Republic. 7. University Hospital Hradec Králové, Hradec Králové, Czech Republic. 8. Dnipropetrovsk City Clinical Hospital No. 4, Dnipropetrovsk, Ukraine. 9. National Cancer Institute, Kiev, Ukraine. 10. University of Debrecen, Faculty of Medicine, Department of Hematology, Debrecen, Hungary. 11. Hospital Universitario 12 de Octubre, Madrid, Spain. 12. Saint John Regional Hospital, University of New Brunswick, St John, New Brunswick, Canada. 13. Barwon Health, University Hospital Geelong, Geelong, Victoria, Australia. 14. Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Istituto di Ricovero e Cura a Carattere Scientifico, Meldola, Italy. 15. Royal Wolverhampton Hospital National Health Service Trust, Wolverhampton, United Kingdom. 16. Nebraska Hematology Oncology, Lincoln, NE. 17. Gachon University Gil Medical Center, Incheon, Republic of Korea. 18. Acerta Pharma (a member of the AstraZeneca group), South San Francisco, CA. 19. Maria Sklodowska-Curie National Institute of Oncology, Kraków, Poland.
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 = 155) or investigator's choice (n = 155; I-R, n = 119; B-R, n = 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 = 44 of 154) treated with acalabrutinib monotherapy, 56% (n = 66 of 118) with I-R, and 26% (n = 9 of 35) with B-R. Deaths occurred in 10% (n = 15 of 154), 11% (n = 13 of 118), and 14% (n = 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.
RCT Entities:
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 = 155) or investigator's choice (n = 155; I-R, n = 119; B-R, n = 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 = 44 of 154) treated with acalabrutinib monotherapy, 56% (n = 66 of 118) with I-R, and 26% (n = 9 of 35) with B-R. Deaths occurred in 10% (n = 15 of 154), 11% (n = 13 of 118), and 14% (n = 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.
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