Expert perspectives on the ALPINE trial of zanubrutinib in patients with relapsed/refractory chronic lymphocytic leukemia.
Andrew H. Lipsky, MD: [The ALPINE trial; NCT03734016] was an international phase 3 trial of zanubrutinib vs ibrutinib in over 650 patients with relapsing refractory CLL [chronic lymphocytic leukemia]. The patients received either zanubrutinib 160 [mg twice a day] or ibrutinib 420 mg daily. The trial assessed the overall response rate with secondary end points including progression-free survival [PFS].
At a median follow-up of 29.6 months, zanubrutinib was found to be superior to ibrutinib with respect to an overall response rate that was 86% vs 75%. More importantly, it also demonstrated an improved progression-free survival. At 24 months the investigator-assessed rates of PFS were 78.4% in the zanubrutinib group, and 65.9% in the ibrutinib group with the hazard ratio for progression of 0.65. And, of course, those outcomes were actually similar when assessed by an independent review committee. Importantly also, among patients with a 17p deletion, a TP53 mutation, or both, the patients who received zanubrutinib also had a longer PFS than those who received ibrutinib with a hazard ratio of 0.53. Also importantly, the safety profile of zanubrutinib was generally 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.
Transcript edited for clarity.