In a phase III trial (BRUIN CLL-314) reported in the Journal of Clinical Oncology, Woyach et al found that pirtobrutinib was associated with a noninferior objective response rate vs ibrutinib in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, while also being associated with favorable trends in interim analysis of progression-free survival.
Study Details
In the open-label trial, 662 Bruton's tyrosine kinase inhibitor–naive patients (intention-to-treat [ITT] population) from sites in 23 countries were randomly assigned between August 2022 and June 2024 to receive pirtobrutinib at 200 mg once daily (n = 331) or ibrutinib at 420 mg once daily (n = 331) until disease progression or unacceptable toxicity. Among these patients, 112 and 113, respectively, were treatment-naive, and 219 and 218, respectively, had relapsed/refractory disease. The primary endpoints of the study were objective response rate on independent review committee assessment in the ITT population and the relapsed/refractory population. The current report provides the prespecified final analysis of objective response, and a descriptive interim analysis of progression-free survival.
Key Findings
In the ITT population, objective response rates were 87.0% (95% confidence interval [CI] = 82.9%–90.4%) in the pirtobrutinib group vs 78.5% (95% CI = 73.7%–82.9%) in the ibrutinib group (ratio = 1.11, 95% CI = 1.03–1.19, P < .0001 for noninferiority). In the R/R population, objective response rates were 84.0% (95% CI = 78.5%–88.6%) in the pirtobrutinib group vs 74.8% (95% CI = 68.5%–80.4%) in the ibrutinib group (ratio = 1.12, 95% CI = 1.02–1.24, P < .0001 for noninferiority).
In the treatment-naive population, objective response rates were 92.9% (95% CI = 86.4%–96.9%) vs 85.8% (95% CI = 78.0%–91.7%).
At a descriptive interim analysis, investigator-assessed progression-free survival favored pirtobrutinib in the ITT population (hazard ratio [HR] = 0.57, 95% CI = 0.39–0.83), relapsed/refractory population (HR= 0.73, 95% CI = 0.47–1.13), and treatment-naive population (HR = 0.24, 95% CI = 0.10–0.59). Rates at 18 months with pirtobrutinib vs ibrutinib were 86.9% vs 82.3% in the ITT population, 81.7% vs 79.2% in the relapsed/refractory population, and 95.3% vs 87.6% in the treatment-naive population.
Grade ≥ 3 adverse events occurred in 54.8% of patients in the pirtobrutinib group vs 53.5% in the ibrutinib group. The most common in both groups included neutropenia (25.3% vs 17.5%), infections (17% vs 16.6%), and pneumonia (6.4% vs 8.6%). Lymphocytosis of any grade occurred in 3.6% vs 5.8% of patients. The pirtobrutinib group had lower rates of any-grade atrial fibrillation/flutter (2.4% vs 13.5%) and hypertension (10.6% vs 15.1%). Adverse events led to discontinuation of treatment in 9.4% vs 10.8% of patients.
The investigators concluded: “Pirtobrutinib demonstrated [noninferiority of objective response rate] vs ibrutinib, with a favorable early [progression-free survival] trend, particularly in treatment-naive patients, and a favorable safety profile including low rates of atrial fibrillation and hypertension.”
Jennifer A. Woyach, MD, of The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Eli Lilly and Company. For full disclosures of the study authors, visit ascopubs.com.
