Brown on Data From the Phase 3 ALPINE Trial of Zanubrutinib in R/R CLL

Jennifer R. Brown, MD, PhD, from the Dana-Farber Cancer Institute, highlights the results from the phase 3 ALPINE study (NCT03734016) evaluating the treatment with zanubrutinib (Brukinsa) for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

According to Brown, the 24-month progression-free survival (PFS) rate was 79.5% with zanubrutinib vs 67.3% with ibrutinib (Imbruvica), and the objective response rate (ORR), which served as the primary end point of the study, was 86.2% with zanubrutinib vs 75.7% with ibrutinib (P = .0007).

Zanubrutinib also led to fewer adverse events resulting in treatment discontinuation (15.4%) vs ibrutinib (22.2%), and no fatal cardiac events were observed with zanubrutinib vs 6 events in the ibrutinib arm.

Transcription:

0:10 | The ALPINE trial is a randomized phase 3 trial comparing the second generation BTK inhibitor zanubrutinib to the first generation one, ibrutinib, in relapsed/refractory patients with CLL. This was an all-comers type population, and patients had a median of 1 prior therapy. About 23% had a 17p deletion or TP53 mutations, and they were randomized between zanubrutinib and ibrutinib until progression or intolerance.

0:41 | The study showed that zanubrutinib had a significant progression-free survival benefit compared with ibrutinib, as measured by both the independent review committee and the investigators for the hazard ratio .65. The 2-year landmark estimates of PFS were 79% for zanubrutinib and 67% for ibrutinib. Furthermore, even in the highest risk group of patients with del(17p) and/or aberrant TP53, a pre-planned analysis of zanubrutinib significantly improved the progression-free survival by 22%, by a larger amount, even in the all-comer population. The finding was consistent across all different types of patient characteristics.

1:24 | There was also a significant safety improvement. Patients on zanubrutinib had fewer serious adverse events, fewer adverse events leading to dose reduction or discontinuation, or interruption, and cardiac events were less as well. There were fewer cardiac serious adverse events, fewer cardiac events leading to drug discontinuation, only 1 on zanubrutinib vs 14 on ibrutinib. There were no cardiac deaths with zanubrutinib vs 6 with ibrutinib. Overall, the study showed that zanubrutinib was more efficacious and safer than ibrutinib.