Pacritinib bests BAT despite study truncation

“Now, it’s important to note,” Dr Mascarenhas said, “that the most common BAT was ruxolitinib, 45%, and hydroxyurea, 19%. And 19% of BAT patients actually had no treatment, watch and wait. This highlights the fact that this is an area where there is really no other viable therapeutic option for these patients.”

Efficacy

Pacritinib-treated patients had significantly greater spleen reduction from baseline to week 24 than BAT-treated patients, with 18% (QD+BID), 15% (QD), and 22% (BID) achieving 35% or more SVR compared to 3% in the BAT arm.

Pacritinib-treated patients also experienced greater TSS reduction, with 25% (QD+BID), 17% (QD), and 32% (BID) reporting 50% or more reduction in TSS compared to 14% in the BAT arm. However, only the PAC BID arm was significantly different from BAT.

SVR in all subgroups—age, gender, JAK2 mutation status, prior treatment, platelet count, hemoglobin, peripheral blasts, and white blood cell count—demonstrated superiority for pacritinib.

Median changes in individual symptom scores were also better in the pacritinib arms than in the BAT arm in almost every category—tiredness, early satiety, abdominal discomfort, inactivity, night sweats, bone pain, and pain under ribs on the left side.

Pruritus was the only category in which BAT was superior, and that was compared to the QD arm and not the BID arm.

The majority of patients who stopped pacritinib therapy were taken off due to the clinical hold.

There were no significant differences between the groups in overall survival. Hazard ratios for overall survival (95% confidence intervals) were 0.68 (0.30, 1.53) for PAC BID vs BAT, 1.18 (0.57, 2.44) for PAC QD vs BAT, and 0.61 (0.27, 1.35) for PAC BID vs QD.

PAC BID maintained this survival advantage compared with BAT across nearly all demographic and myelofibrosis-associated risk factors.

Patients who were red blood cell transfusion-dependent at baseline experienced a statistically significant decrease in transfusion frequency from baseline to week 24 in both the QD and BID pacritinib arms compared with BAT.

And thrombocytopenia was not a significant factor for patients who were receiving pacritinib and had platelet counts less than 50,000/μL.

Toxicity

The most common treatment-emergent adverse events (AEs) associated with pacritinib were diarrhea, nausea, vomiting, anemia, and thrombocytopenia. They were generally less frequent for BID compared with QD administration.

The most common serious adverse events (SAEs)—occurring in 5% of patients or more in any arms—were anemia (5%, 8%, and 3%), thrombocytopenia (2%, 6%, and 2%), pneumonia (5%, 6%, and 4%), and acute renal failure (5%, 2%, and 2%) in the QD, BID, and BAT arms, respectively.

SAEs of interest included congestive heart failure, atrial fibrillation, cardiac arrest, epistaxis, and subdural hematoma, which occurred in 3% or fewer patients in any arm.

“They [the SAEs] were relatively infrequent, and there was not a clear signal of toxicity,” Dr Mascarenhas said.

Deaths

Deaths in the intent-to-treat evaluable population were censored at the time of full clinical hold.

For the entire enrolled population, 15/104 deaths occurred in the QD arm, 10/107 in the BID arm, and 14/100 in the BAT arm.

After the full clinical hold, 7, 10, and 6 deaths occurred in the QD, BID, and BAT arms, respectively.

Seven of 20 patients died after crossover to pacritinib. Five were due to AEs—3 cardiac, 1 bleeding, and 1 other.

“It’s important to note that progression of disease was the leading cause of death in the PAC BID arm,” Dr Mascarenhas noted. “This is after the patients stopped the drug [when the trial was on clinical hold].”