Pacritinib bests BAT despite study truncation
SAN DIEGO—The JAK2/FLT3 inhibitor pacritinib significantly reduces spleen volume and symptoms in patients with myelofibrosis and low platelet counts,
compared to best available therapy (BAT), according to results of the PERSIST-2 trial.
In this phase 3 trial, BAT included the JAK1/2 inhibitor ruxolitinib. And pacritinib demonstrated benefits over BAT despite a truncated trial.
The US Food and Drug Administration (FDA) placed PERSIST-2 on clinical hold in February 2016 due to concerns over interim survival results, bleeding, and cardiovascular events.
Patients randomized at least 22 weeks prior to the clinical hold contributed data to the week 24 endpoint, the results of which were presented at the 2016 ASH Annual Meeting.
John Mascarenhas, MD, of Icahn School of Medicine at Mount Sinai in New York, New York, delivered the results as a late-breaking abstract (LBA-5).
Ruxolitinib is FDA-approved to treat myelofibrosis, but it is associated with dose-limiting cytopenias and is not indicated for patients with platelet counts less than 50,000/μL.
The earlier PERSIST-1 trial demonstrated sustained spleen volume reduction (SVR) and symptom control with pacritinib therapy regardless of baseline platelet count, but it did not include ruxolitinib in the BAT arm.
PERSIST-2 study design
Patients were randomized on a 1:1:1 basis to pacritinib at 400 mg once daily (PAC QD), pacritinib at 200 mg twice daily (PAC BID), or BAT, including ruxolitinib.
Patients had to have primary or secondary myelofibrosis and platelet counts of 100,000/μL or less. Patients were allowed to have had prior JAK2 inhibitors.
Crossover from BAT was allowed after progression at any time or at week 24.
The study had 2 primary endpoints: percent of patients achieving a 35% or greater SVR and the percent of patients achieving a 50% or more reduction in total symptom score (TSS) by MPN-SAF TSS 2.0.
The primary study objective was the efficacy of pooled QD and BID pacritinib compared to BAT. The secondary objective was the efficacy of QD or BD separately compared to BAT.
Patient demographics
The study randomized 311 patients, and 221 were included in the intent-to-treat efficacy population.
The efficacy population consisted of all patients randomized prior to September 7, 2015, which allowed their data to be included in the week 24 endpoint analysis prior to the clinical hold.
The PAC QD arm consisted of 75 patients with a median age of 69 (range, 39-85). Seventy-one percent were 65 or older, and about half were male.
About three-quarters had an ECOG performance status of 0-1, 61% had primary myelofibrosis, 21% had primary polycythemia vera (PPV), and 17% had primary essential thrombocythemia (PET). About half were DIPSS Intermediate-2 risk, 80% were JAK2V617F positive, and 51% had a platelet count less than 50,000/μL.
The PAC BID arm consisted of 74 patients with a median age of 67 (range, 39-85). Sixty-two percent were 65 or older, and 65% were male.
Eighty-eight percent had an ECOG performance status of 0-1, 74% had primary myelofibrosis, 19% had PPV, and 7% had PET. About half were DIPSS Intermediate-2 risk, 80% were JAK2V617F positive, and 42% had a platelet count less than 50,000/μL.
The BAT arm consisted of 72 patients with a median age of 69 (range, 32-83). Seventy-one percent were 65 or older, and about half were male.
Three-quarters had an ECOG performance status of 0-1, 60% had primary myelofibrosis, 22% had PPV, and 18% had PET. About half were DIPSS Intermediate-2 risk, 71% were JAK2V617F positive, and 44% had a platelet count less than 50,000/µL.
Prior ruxolitinib therapy was consistent across the arms—41.3% (PAC QD), 42% (PAC BID), and 46% (BAT).
