{"entity":{"id":"paper-zanubrutinib-cll-n-engl-j-med-2023","kind":"paper","name":"Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia","aka":[],"tldr":"Phase 2 or 3 results paper on Zanubrutinib in Chronic lymphocytic leukaemia, in New England Journal of Medicine (2023), one of the most cited Europe PMC records with Zanubrutinib in its title.","summary":"Background: In a multinational, phase 3, head-to-head trial, ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, was compared with zanubrutinib, a BTK inhibitor with greater specificity, as treatment for relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). In prespecified interim analyses, zanubrutinib was superior to ibrutinib with respect to overall response (the primary end point). Data from the final analysis of progression-free survival are now available.\n\nMethods: We randomly assigned, in a 1:1 ratio, patients with relapsed or refractory CLL or SLL who had received at least one previous course of therapy to receive zanubrutinib or ibrutinib until the occurrence of disease progression or unacceptable toxic effects. In this final analysis, progression-free survival (a key secondary end point) was assessed with the use of a hierarchical testing strategy to determine whether zanubrutinib was noninferior to ibrutinib. If noninferiority was established, the superiority of zanubrutinib was assessed and claimed if the two-sided P value was less than 0.05.\n\nResults: At a median follow-up of 29.6 months, zanubrutinib was found to be superior to ibrutinib with respect to progression-free survival among 652 patients (hazard ratio for disease progression or death, 0.65; 95% confidence interval, [CI], 0.49 to 0.86; P = 0.002), as assessed by the investigators; the results were similar to those as assessed by an independent-review committee. At 24 months, the investigator-assessed rates of progression-free survival were 78.4% in the zanubrutinib group and 65.9% in the ibrutinib group. Among patients with a 17p deletion, a TP53 mutation, or both, those who received zanubrutinib had longer progression-free survival than those who received ibrutinib (hazard ratio for disease progression or death, 0.53; 95% CI, 0.31 to 0.88); progression-free survival across other major subgroups consistently favored zanubrutinib. The percentage of patients with an overall response was higher in the zanubrutinib group than in the ibrutinib group. The safety profile of zanubrutinib was better than that of ibrutinib, with fewer adverse events leading to treatment discontinuation and fewer cardiac events, including fewer cardiac events leading to treatment discontinuation or death.\n\nConclusions: In patients with relapsed or refractory CLL or SLL, progression-free survival was significantly longer among patients who received zanubrutinib than among those who received ibrutinib, and zanubrutinib was associated with fewer cardiac adverse events. (Funded by BeiGene; ALPINE ClinicalTrials.gov number, NCT03734016.).\n\nIndexed on Europe PMC as PubMed record 36511784 (DOI 10.1056/nejmoa2211582). Its title names Zanubrutinib and its text names Chronic lymphocytic leukaemia; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Research Support, Non-U.S. Gov't, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"MRD-guided treatment duration in CLL\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/nejmoa2211582"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36511784/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36511784"},{"label":"ClinicalTrials.gov NCT03734016","url":"https://clinicaltrials.gov/study/NCT03734016"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["alpine"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/nejmoa2211582","pmid":"36511784","authors":"Brown JR, Eichhorst B, Hillmen P, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Zanubrutinib in Chronic lymphocytic leukaemia, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Zanubrutinib in the title and Chronic lymphocytic leukaemia in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},"route":"/key-papers/paper-zanubrutinib-cll-n-engl-j-med-2023/","neighbours":{"trial":[{"id":"alpine","kind":"trial","name":"ALPINE","route":"/trials/alpine/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"idea":[{"id":"idea-mrd-guided-stop-cll","kind":"idea","name":"MRD-guided treatment duration in CLL","route":"/ideas/idea-mrd-guided-stop-cll/"}]}}