Positive Results Reported for Panobinostat in Pivotal Myeloma Trial
Investigators report improvement in progression-free survival
Positive results have been reported from a pivotal phase III trial of panobinostat (LBH589, Novartis), an investigational oral pan-inhibitor of class I, II, and IV histone (and non-histone) deacetylase (DAC) enzymes, in patients with multiple myeloma.
Treatment with panobinostat in combination with bortezomib and dexamethasone achieved a 37% improvement in progression-free survival (PFS) compared with treatment with bortezomib and dexamethasone plus placebo in patients with relapsed or relapsed/refractory multiple myeloma, meeting the study’s primary endpoint (hazard ratio, 0.63; P < 0.0001).
Results from the PANORAMA-1 (PANobinostat ORAl in Multiple MyelomA-1) trial were presented June 2 at the 50th annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.
A 4-month prolongation of median PFS was observed in the panobinostat arm compared with the placebo arm (12 months vs. 8 months, respectively). Panobinostat had an effect across all patient subgroups (for example, by age or prior exposure to bortezomib or immunomodulatory therapy). The study’s findings also showed that adding panobinostat to bortezomib and dexamethasone led to a significant increase in higher-quality responses compared with standard-of-care therapy alone, as evidenced by a nearly two-fold increase in the rates of complete or near-complete responses (28% vs. 16%, respectively; P = 0.00006).
Adverse events (AEs) were consistent with those previously seen in studies of panobinostat. The most common grade-3 or grade-4 AEs in the panobinostat combination arm compared with the placebo arm were thrombocytopenia (67% vs. 31%, respectively), lymphopenia (53% vs. 40%), neutropenia (35% vs. 11%), and diarrhea (26% vs. 8%). AEs were generally manageable through supportive care and dose reductions.
Additional data from the PANORAMA-1 trial will be presented June 14 at the 19th Congress of the European Hematology Association in Milan, Italy.
The FDA granted “priority review” status to panobinostat in May 2014. This designation is given to therapies that offer major advances in treatment.
PANORAMA-1 is a phase III randomized, double-blind, placebo-controlled, global registration trial to evaluate panobinostat in combination with bortezomib and dexamethasone compared with bortezomib and dexamethasone alone in a total of 768 patients with relapsed or relapsed and refractory multiple myeloma who failed on at least one prior treatment. Data for overall survival, the key secondary endpoint of the trial, are not yet mature. Other secondary endpoints include the overall response rate, the duration of response, and safety.
Because panobinostat is an investigational compound, its safety and efficacy profiles have not yet been established. The drug can be accessed only through clinical trials.
Multiple myeloma typically occurs in individuals 50 years of age and older, with few cases in individuals younger than 40. Common symptoms include a high level of calcium in the blood, a decreased number of red blood cells, kidney failure, bone damage, pain, and fatigue, but these symptoms may vary from person to person. The 4-year survival rate is 44%. No curative therapies are currently available for the disease.
Source: Novartis; June 2, 2014.