ALPINE

ALPINE, trial NCT03734016 sponsored by BeOne, formerly BeiGene, and published in the New England Journal of Medicine in 2023, was the first head-to-head trial in which a newer BTK inhibitor was both safer and more effective than ibrutinib in relapsed or refractory chronic lymphocytic leukaemia. It randomised 652 patients to zanubrutinib or ibrutinib, met its primary progression-free survival endpoint including in del(17p) and TP53 disease, produced a higher response rate, less than half the rate of atrial fibrillation and fewer discontinuations, and the three-year update maintained the advantage. OnCo links it to chronic lymphocytic leukaemia, BTK as a target, zanubrutinib, ibrutinib, John Oyler, Jennifer R. Brown and the caution pairing about ibrutinib in patients with cardiac risk. Whether that superiority reflects the drug or the trial is the open question.