KEY TAKEAWAYS
- In the phase 3 head-to-head trial ((ALPINE)), zanubrutinib demonstrated superior progression-free survival compared to ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
- At 24 months, the progression-free survival rate was 78.4% for zanubrutinib and 65.9% for ibrutinib.
- Patients with a 17p deletion, a TP53 mutation, or both had improved outcomes with zanubrutinib compared to ibrutinib (HR 0.53; 95% CI, 0.31 to 0.88).
- Zanubrutinib had a better safety profile than ibrutinib, with fewer adverse events leading to treatment discontinuation and fewer cardiac events.
In a head-to-head study involving patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib was compared to the more selective BTK inhibitor zanubrutinib. The predetermined interim analysis showed that zanubrutinib outperformed ibrutinib in total response (the primary endpoint). The results of the complete analysis of progression-free survival are now available.
Patients with relapsed or refractory CLL or SLL who had already undergone at least 1 prior therapy were randomly assigned to receive either zanubrutinib or ibrutinib until disease progression or intolerable adverse effects occurred. In this last analysis, a hierarchical testing technique was used to compare zanubrutinib with ibrutinib for its effects on progression-free survival, an important secondary endpoint. Zanubrutinib’s superiority was evaluated, and if the two-sided P value was less than 0.05, it was reported to be superior to the control group.
About 652 patients were followed for a median of 29.6 months, and the investigators found that zanubrutinib was superior to ibrutinib in terms of progression-free survival (hazard ratio for disease progression or death, 0.65; 95% confidence interval, [CI], 0.49 to 0.86; P = 0.002). The results were consistent with those found by an independent review committee. After 24 months, the zanubrutinib group had a 78.4% progression-free survival rate compared to the ibrutinib group’s 65.9% rate (as determined by the study’s investigators). All main subgroups saw longer progression-free survival with zanubrutinib than with ibrutinib. This was especially true for patients with a 17p deletion, TP53 mutation, or both (hazard ratio for disease progression or death, 0.53; 95% CI, 0.31 to 0.88). The zanubrutinib group had a more significant proportion of patients who experienced an overall response than the ibrutinib group. Compared to ibrutinib, zanubrutinib was associated with a better safety profile, with fewer cardiac events and fewer adverse events resulting in treatment termination or death.
Treatment with zanubrutinib was linked with significantly longer progression-free survival, and fewer cardiac adverse events in patients with relapsed or refractory CLL or SLL compared to treatment with ibrutinib.
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03734016
Brown J, Eichhorst B, Hillmen P, Jurczak W, Kaźmierczak M, Lamanna N, O’Brien S, Tam C, Qiu L, Zhou K, Simkovic M, Mayer J, Gillespie-Twardy A, Ferrajoli A, Ganly P, Weinkove R, Grosicki S, Mital A, Robak T, Osterborg A, Yimer H, Salmi T, Wang M, Fu L, Li J, Wu K, Cohen A, Shadman M. Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia. N Engl J Med. 2023 Jan 26;388(4):319-332. doi: 10.1056/NEJMoa2211582. Epub 2022 Dec 13. PMID: 36511784.
