In MCL, indirect comparison found zanubrutinib had better PFS and OS than acotinib

Based on published results, Bruton's tyrosine kinase (BTK) inhibitor zanubrutinib (Brukinsa; BeOne Analysis of separate trials of Acalabrutinib (Calquence; AstraZeneca) and Acalabrutinib (Calquence; AstraZeneca) found that /span>Zanubrutinib was associated with "significant improvements" in progression-free survival (PFS) and overall survival (OS) in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL; non-Hodgkin lymphoma). Sham treatment comparison (STC) found that zanubrutinib was associated with improved P FS (HR, 0.57; 95% CI, 0.35-0.94; P = 0.0272) was associated with OS (HR, 0.43; 95% CI, 0.23-0.82; P = 0.0105). Overall response rate (ORR) numerically favored zanubrutinib but did not reach statistical significance.

STC is one of several indirect analytical methods that can be used to evaluate drugs of the same class that are not compared in clinical trials. Although the study authors note that clinical trials remain the gold standard, the current study [provides] much-needed evidence of the comparative efficacy of zanubrutinib and acotinib in R/R MCL in the absence of head-to-head trials. BeOne Medicines supports this research.

Despite recent progress in clinical trials, MCL has a poor prognosis, with a median OS of 3 to 5 years. Zanubrutinib and acotinibare both second-generationBTK inhibitors that have shown efficacy and safety in single-arm trials involving patients with R/R MCL. The author cited the single-arm experimental data of zanubrutinib, which showed that the ORR was 84% u200bu200band the complete response (CR) was 78% in a median of 35.3 months, while the ORR of acotinib was 81.5%, the CR was 47.6%, and the median was 38.1 months. However, due to the lack of comparative effectiveness data, the authors chose the STC method because it is particularly suitable for settings with limited patient data, such as MCL.

Study authors fromTen potential trials were initiated and 3 were found to meet the analysis criteria; excluded trials evaluated untreated MCL, combined use of investigational drugs, or ongoing trials. The team then conducted a 3-part process of STC using trial data extracted from 3 studies. Overall, aside from some differences, all 3 studies had enough similarities for comparison. Where feasible, differences expected to affect the results were adjusted in the analyses.

The authors noted some differences between the trials and how they were interpreted. Patients in the zanubrutinib trial appeared to be younger, with a smaller proportion of patients under the age of 65. One of the two trials of zanubrutinib was conducted only in China, and most of the patients in the other trial were from Australia and New Zealand. Sensitivity analyzes excluding the age and race covariates showed that these covariates had no effect on the results. Sensitivity analyzes excluding the age and race covariates demonstrated that these variables did not affect treatment outcomes.

There were some differences in practice patterns based on where patients lived, with more U.S. patients receiving autologous stem cell transplants and more of them enrolled in acotinib trials. Some information is not available. Several studies have shown that tumor protein p53 (TP53) gene mutations and Ki-67 index have a poor prognostic impact on MCL patients. Because baseline data for TP53 mutations and Ki-67 index covariates in the acotinib trial were not available, we did not adjust for these prognostic variables in our analyses.

The authors reviewed previous statistical analyzes comparing2 BTK inhibitors to other therapies and noted that no safety comparison was performed, but a meta-analysis may provide better insights. After adjusting for a large number of covariates, zanubrutinib "produced significantly better PFS and OS than acotinib in patients with R/R MCL." Since head-to-head trials are unlikely, STC may support evidence-based treatment decisions and optimize care for patients with this disease.

Reference materials:https://www.ajmc.com/view/indirect-comparison-finds-zanubrutinib-associated-with-better-pfs-os-than-acalabrutinib-in-mcl