Photo courtesy of Novartis
The European Commission has approved panobinostat (Farydak) for use in combination with other agents to treat patients with relapsed and/or refractory
multiple myeloma (MM).
The histone deacetylase (HDAC) inhibitor is now approved, in combination with bortezomib and dexamethasone, to treat adults with MM who have received at least 2 prior treatment regimens, including bortezomib and an immunomodulatory agent (IMiD).
The approval marks the first time an HDAC inhibitor with epigenetic activity is available in the European Union (EU). The approval applies to all 28 EU member states plus Iceland, Norway, and Liechtenstein.
The European Commission approved panobinostat based on results of a subgroup analysis of 147 patients in the phase 3 PANORAMA-1 trial.
PANORAMA-1 was a randomized, double-blind, placebo-controlled trial of 768 MM patients. The study showed that, overall, panobinostat plus bortezomib and dexamethasone increased progression-free survival (PFS) by about 4 months when compared to placebo plus bortezomib and dexamethasone.
Full results of the PANORAMA-1 study were published in The Lancet Oncology last year. Results from the substudy of 147 patients were presented at ASCO 2015.
The 147 patients had relapsed or relapsed and refractory MM and had received 2 or more prior regimens, including bortezomib and an IMiD.
The median PFS benefit in this subgroup increased by 7.8 months in the panobinostat arm compared to the placebo arm. The median PFS was 12.5 months (n=73) and 4.7 months (n=74), respectively (hazard ratio=0.47).
Common grade 3/4 non-hematologic adverse events in the panobinostat arm and placebo arm, respectively, included diarrhea (33.3% vs 15.1%), asthenia/fatigue (26.4% vs 13.7%), and peripheral neuropathy (16.7% vs 6.8%).
The most common grade 3/4 hematologic events in the panobinostat arm and placebo arm, respectively, were thrombocytopenia (68.1% vs 44.4%), lymphopenia (48.6% vs 49.3%), and neutropenia (40.3% vs 16.4%).
Cardiac events (most frequently atrial fibrillation, tachycardia, palpitation, and sinus tachycardia) were reported in 17.6% of panobinostat-treated patients and 9.8% of placebo-treated patients. Syncope was reported in 6.0% and 2.4%, respectively.
The percentage of on-treatment deaths was similar in the panobinostat and placebo arms—6.9% and 6.8%, respectively. But on-treatment deaths not due to the study indication (MM) were reported in 6.8% and 3.2% of patients, respectively.
Panobinostat in combination with bortezomib and dexamethasone is also approved in the US, Chile, and Japan for certain patients with previously treated MM. The exact indication for panobinostat varies by country.
