TABLE.
Summary of the Intention-to-Treat Efficacy Population (From Baseline to Week 24)
Pacritinib 400 mg Once-Daily
(n=75) Pacritinib 200 mg Twice-Daily
(n=74) BAT
(n=72)
Patients achieving ≥35% SVR 11 (15%) 16 (22%) 2 (3%)
Patients achieving ≥50% reduction in TSS 13 (17%) 24 (32%) 10 (14%)
Overall
Patients With Prior Ruxolitinib
n=31 n=31 n=33
Patients achieving ≥35% SVR 2 (6%) 4 (13%) 1 (3%)
Patients achieving ≥50% reduction in TSS 3 (10%) 10 (32%) 5 (15%)
Patients With Baseline Platelets <50×10 9 /L
n=38 n=31 n=32
Patients achieving ≥35% SVR 7 (18%) 9 (29%) 1 (3%)
Patients achieving ≥50% reduction in TSS 6 (16%) 7 (23%) 4 (13%)
BAT = best-available therapy; SVR = spleen volume reduction; TSS = total symptom score
SVR in the pacritinib cohort did not differ based on sex,
age, JAK2 V617F status, prior treatment with JAK2 inhibitors,
or baseline cytopenias.
Overall survival was not significantly different between
the three groups:
• hazard ratio (HR) = 1.18 (95% CI 0.57-2.44) for BAT vs.
pacritinib once-daily
• HR = 0.68 (95% CI 0.30-1.53) for BAT vs. pacritinib
twice-daily (p values not reported)
In the BAT cohort, the overall mortality rate was lower among
those who crossed over to receive pacritinib, compared with
those who did not (n=4 [8%] vs. n=10 [20%]; p value not
reported). On-study deaths occurred in six patients receiving
pacritinib twice-daily, 14 receiving pacritinib once-daily, and
nine receiving BAT.
The most common non-hematologic AEs associated
with pacritinib were gastrointestinal (GI) events, fatigue,
peripheral edema, and dizziness, while the most common in
the BAT cohort were abdominal pain, fatigue, diarrhea, and
peripheral edema.
“Pacritinib was well tolerated and GI toxic effects were
generally low-grade, less frequent with twice-daily dosing, and
rarely led to treatment discontinuation,” the authors reported.
“Clinical improvement in hemoglobin and reduction in trans-
fusion requirements were also more frequent in patients who
received pacritinib, particularly with twice-daily dosing.”
Regarding the AEs that led to the initial clinical hold, the
researchers observed a potential increased risk of grade 3 or
4 bleeding in the pacritinib twice-daily cohort (15 patients
[14%]), compared with the other cohorts (7 patients [7%]
in both the pacritinib once-daily and BAT groups). This
association “appeared to be independent of platelet count,”
they noted.
The rate of grade 3 or 4 cardiac events was also lowest
with twice-daily pacritinib, and no cardiac failure or deaths
due to cardiac events occurred in this group.
The study is limited by its truncated length (owing to the
clinical hold), which hinders the ability to evaluate efficacy
and safety and reduces evaluable sample size. Time-to-event
analyses were also confounded by patient crossover.
Pacritinib represents an effective treatment option for MF
and thrombocytopenia, including in those with prior JAK2
treatment such as ruxolitinib, the researchers concluded.
The ongoing phase II PAC203 trial will examine pacritinib at
lower dose levels (100 mg once- or twice-daily and 200 mg
twice-daily) in patients with MF and thrombocytopenia who
were previously treated with ruxolitinib.
CTI BioPharma provided funding for the study. ●
The corresponding authors report financial support from
CTI BioPharma, Incyte, and Promedior. CTI BioPharma
provided editorial support.
REFERENCE
Mascarenhas J, Hoffman R, Talpaz M, et al. Pacritinib vs best available therapy,
including ruxolitinib, in patients with myelofibrosis: a randomized clinical trial.
JAMA Oncol. 2018 March 8. [Epub ahead of print]
May 2018
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