PMID- 29533000 OWN - NLM STAT- MEDLINE DCOM- 20190807 LR - 20240314 IS - 2045-7634 (Electronic) IS - 2045-7634 (Linking) VI - 7 IP - 4 DP - 2018 Apr TI - Ibrutinib versus rituximab in relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma: a randomized, open-label phase 3 study. PG - 1043-1055 LID - 10.1002/cam4.1337 [doi] AB - In the Asia-Pacific region, treatment options are limited for patients with relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Rituximab is widely used in this setting when purine analog-based therapies are not appropriate. We evaluated the efficacy and safety of ibrutinib compared with rituximab in a randomized, open-label phase 3 study in predominantly Asian patients with relapsed/refractory CLL/SLL. Patients (N = 160) were randomly assigned 2:1 to receive 420 mg ibrutinib (n = 106) until disease progression (PD) or unacceptable toxicity or up to six cycles of rituximab (n = 54). The primary endpoint was investigator-assessed progression-free survival (PFS); key secondary endpoints were overall response rate (ORR), overall survival (OS), and safety. Rituximab-treated patients could crossover to receive ibrutinib after confirmed PD. At data cutoff, median treatment duration was 16.4 months for ibrutinib and 4.6 months for rituximab. Ibrutinib significantly improved PFS (hazard ratio [HR] = 0.180, 95% confidence interval [CI]: 0.105-0.308). ORR was significantly higher (P < 0.0001) with ibrutinib (53.8%) than with rituximab (7.4%). At a median follow-up of 17.8 months, ibrutinib improved OS compared with rituximab (HR = 0.446; 95% CI: 0.221-0.900; P = 0.0206). Overall incidence of adverse events (AEs) was similar between treatments and was not exposure-adjusted. With ibrutinib, most common AEs were diarrhea and platelet count decreased; with rituximab, most common AEs were neutrophil count decreased and platelet count decreased. Grade >/=3 AEs were reported in 82.7% of ibrutinib-treated patients and 59.6% of rituximab-treated patients. Ibrutinib improved PFS, ORR, and OS compared with rituximab and displayed a manageable safety profile in Asian patients with relapsed/refractory CLL/SLL. CI - (c) 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. FAU - Huang, Xiaojun AU - Huang X AUID- ORCID: 0000-0003-1906-5819 AD - Peking University People's Hospital, Beijing, China. FAU - Qiu, Lugui AU - Qiu L AD - Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, China. FAU - Jin, Jie AU - Jin J AD - The First Affiliated Hospital, Zhejiang University College of Medicine, Zhejiang, China. FAU - Zhou, Daobin AU - Zhou D AD - Peking Union Medical College Hospital, Beijing, China. FAU - Chen, Xiequn AU - Chen X AD - Xijing Hospital, Shanxi, China. FAU - Hou, Ming AU - Hou M AD - Qilu Hospital of Shandong University, Jinan, China. FAU - Hu, Jianda AU - Hu J AD - Fujian Medical University Union Hospital, Fuzhou, China. FAU - Hu, Yu AU - Hu Y AUID- ORCID: 0000-0002-2815-4568 AD - Wuhan Union Hospital, Wuhan, China. FAU - Ke, Xiaoyan AU - Ke X AD - Peking University Third Hospital, Beijing, China. FAU - Li, Junmin AU - Li J AD - Ruijin Hospital, Shanghai, China. FAU - Liang, Yingmin AU - Liang Y AD - Tangdu Hospital, Shanxi, China. FAU - Liu, Ting AU - Liu T AD - West China Hospital, Chengdu, China. FAU - Lv, Yue AU - Lv Y AD - Sun Yat-Sen University Cancer Center, Guangzhou, China. FAU - Ren, Hanyun AU - Ren H AD - Peking Union Medical College Hospital, Beijing, China. FAU - Sun, Aining AU - Sun A AD - The First Affiliated Hospital of Soochow University, Suzhou, China. FAU - Wang, Jianmin AU - Wang J AD - Changhai Hospital, The Second Military Medical University, Shanghai, China. FAU - Zhao, Chunting AU - Zhao C AD - The Affiliated Hospital of Qingdao University Medical College, Qingdao, China. FAU - Salman, Mariya AU - Salman M AD - Janssen Research & Development, Raritan, New Jersey. FAU - Sun, Steven AU - Sun S AD - Janssen Research & Development, Raritan, New Jersey. FAU - Howes, Angela AU - Howes A AD - Janssen Research & Development, High Wycombe, UK. FAU - Wang, Jingzhao AU - Wang J AD - Janssen China Research & Development Center, Beijing, China. FAU - Wu, Peng AU - Wu P AD - Janssen China Research & Development Center, Beijing, China. FAU - Li, Jianyong AU - Li J AD - Jiangsu Province Hospital, Nanjing, China. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20180313 PL - United States TA - Cancer Med JT - Cancer medicine JID - 101595310 RN - 0 (Piperidines) RN - 0 (Pyrazoles) RN - 0 (Pyrimidines) RN - 1X70OSD4VX (ibrutinib) RN - 4F4X42SYQ6 (Rituximab) RN - JAC85A2161 (Adenine) MH - Adenine/analogs & derivatives MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Drug Resistance, Neoplasm MH - Female MH - Humans MH - Kaplan-Meier Estimate MH - Leukemia, Lymphocytic, Chronic, B-Cell/*drug therapy/mortality/*pathology MH - Male MH - Piperidines MH - Proportional Hazards Models MH - Pyrazoles/administration & dosage MH - Pyrimidines/administration & dosage MH - Recurrence MH - Retreatment MH - Rituximab/administration & dosage MH - Treatment Outcome PMC - PMC5911578 OTO - NOTNLM OT - Asia-Pacific OT - chronic lymphocytic leukemia OT - ibrutinib OT - rituximab OT - small lymphocytic lymphoma EDAT- 2018/03/14 06:00 MHDA- 2019/08/08 06:00 PMCR- 2018/03/13 CRDT- 2018/03/14 06:00 PHST- 2017/09/22 00:00 [received] PHST- 2017/12/18 00:00 [revised] PHST- 2017/12/19 00:00 [accepted] PHST- 2018/03/14 06:00 [pubmed] PHST- 2019/08/08 06:00 [medline] PHST- 2018/03/14 06:00 [entrez] PHST- 2018/03/13 00:00 [pmc-release] AID - CAM41337 [pii] AID - 10.1002/cam4.1337 [doi] PST - ppublish SO - Cancer Med. 2018 Apr;7(4):1043-1055. doi: 10.1002/cam4.1337. Epub 2018 Mar 13.