Progression-free survival and overall response rates greatly improved in patients with CLL/SLL treated with Brukinsa compared with Imbruvica.
The risk for disease progression or death was reduced by 35% in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who were treated with Brukinsa (zanubrutinib) compared with Imbruvica (ibrutinib), according to recent study findings.
Results from the phase 3 ALPINE study were presented at the 2022 ASH Annual Meeting and simultaneously published in the New England Journal of Medicine.
The 24-month progression-free survival (time from treatment until disease worsens) rate was 79.5% with Brukinsa compared with 67.3% with Imbruvica. The objective response rate (percentage of patients whose disease shrunk as a result of treatment), which was the primary focus of the study, was 86.2% with Brukinsa compared with 75.7% for Imbruvica.
There were fewer side effects that led to treatment discontinuation observed with Brukinsa (15.4%) versus Imbruvica (22.2%). Atrial fibrillation/flutter (heart rhythm abnormalities) was significantly less common with Brukinsa (5.2%) versus Imbruvica (13.3%). There were no fatal cardiac events reported with Brukinsa compared with six events in the Imbruvica group.
“ALPINE is the first study to demonstrated (progression-free survival) superiority in a head-to-head comparison of BTK inhibitors in patients with relapsed or refractory CLL or SLL. (Brukinsa) has now proven superiority to (Imbruvica) in both (progression-free survival) and (objective response rate),” lead study author Dr. Jennifer R. Brown, from the Dana-Farber Cancer Institute in Boston, said during a presentation of the results. “(Brukinsa) has a better cardiac profile than (Imbruvica), with lower rates of atrial fibrillation, serious cardiac events, cardiac events leading to treatment discontinuation and fatal cardiac events.”
In the ALPINE study, 652 patients with relapsed or refractory CLL/SLL were randomized to receive Brukinsa (327 patients) or Imbruvica (325 patients).
Fifty-three patients in this group discontinued due to side effects and 24 discontinued due to progressive disease. In the Imbruvica arm, one patient did not receive treatment, 74 discontinued due to side effects and 42 discontinued due to progressive disease.
After 29.6 months of follow up, the median PFS was not yet reached in the Brukinsa arm compared with 35 months with Imbruvica. In patients with del(17p) or TP53 mutations (75 patients in each arm), the 24-month progression-free survival rates were 77.6% versus 55.7% for Brukinsa and Imbruvica, respectively. Progression-free survival favored Brukinsa across other major subgroups analyzed.
A side effect of any grade or cause was experienced by 98.1% of patients in the Brukinsa group and by 99.1% of those in the Imbruvica group. Severe to fatal side effects were seen in 67.3% of those treated with Brukinsa, with 10.2% of patients having fatal side effects. In the Imbruvica group, 70.4% of patients experienced a severe to fatal side effect, with fatal events seen in 11.1% of patients.
Serious side effects were experienced by 42% and 50% of patients in the Brukinsa and Imbruvica groups, respectively.
The median treatment duration was 28.4 months with Brukinsa versus 24.3 months for Imbruvica. Side effects led to a dose reduction for 12.3% of those in the Brukinsa arm and for 17% of those in the Imbruvica group. Dose interruptions were required due to side effects in 50% and for 56.8% of patients in the Brukinsa and Imbruvica arms, respectively.
Heart-related side effects were experienced by 21.3% and 29.6% of those in the Brukinsa and Imbruvica groups, respectively. Serious heart-related side effects were experienced by six patients in the Brukinsa group (1.9%) compared with 25 in the Imbruvica group (7.7%). Of these patients, two in the Brukinsa group and 16 in the Imbruvica group had no previous cardiac-related medical history.
“Overall, safety was improved with (Brukinsa), with serious (side effects) reduced with (Brukinsa), and (side effects) leading to dose reduction, dose interruption and discontinuation lower with (Brukinsa) versus (Imbruvica),” Brown said.
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