Phase III PANORAMA-1 trial subgroup analysis for Farydak (panobinostat) for multiple myeloma- Novartis

Novartis has presented results from a pivotal Phase III clinical trial exploratory subgroup analysis showing a 7.8-month improvement in median progression-free survival (PFS) when using Farydak (panobinostat, previously known as LBH589) in combination with bortezomib (Velcade) and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma who had received two or more prior regimens, including bortezomib and an immunomodulatory agent (IMiD). Findings are being presented in an oral session at the 20th Congress of the European Hematology Association (EHA) in Vienna. These data are from a subgroup analysis of 147 patients with relapsed or relapsed and refractory multiple myeloma who had received two or more prior regimens, including bortezomib and an IMiD, in the Phase III, randomized, double-blind, placebo-controlled, multicenter global registration trial called PANORAMA-1 (PANobinostat ORAl in Multiple MyelomA). This subgroup excluded patients who received only one prior regimen.

The analysis showed that in this subgroup, median PFS increased to 12.5 months in the panobinostat-treatment arm compared to 4.7 months in the placebo plus bortezomib and dexamethasone arm (hazard ratio=0.47 [95% confidence interval (CI), 0.31-0.72]). Treatment with panobinostat in combination with bortezomib and dexamethasone when compared to the placebo arm also led to an increase in complete/near complete response rates (21.9% versus 8.1%) and overall response rate (58.9% versus 39.2%). Common grade 3/4 non-hematologic adverse events (AEs) in the panobinostat-treatment arm compared to the placebo arm for this subgroup included diarrhea (33.3% versus 15.1%), asthenia/fatigue (26.4% versus 13.7%) and peripheral neuropathy (16.7% versus 6.8%). The most common grade 3/4 hematologic laboratory abnormalities in the panobinostat-treatment arm compared to the placebo arm were thrombocytopenia (68.1% versus 44.4%), lymphopenia (48.6% versus 49.3%) and neutropenia (40.3% versus 16.4%). The percentage of on-treatment deaths in the panobinostat-treatment arm compared to the placebo arm in this subgroup was similar (6.9% versus 6.8%).

Comment: Panobinostat has an accelerated approval from the FDA conditional on the positive results of additional trials. It was initially rejected in November 2014 as its side effects were considered too severe. Panobinostat, bortezomib and the steroid dexamethasone prolonged progression-free survival (PFS) by 3.9 months compared to the other drugs on their own, helping patients live a median of one year without a major event. At the same time, 7% of patients in the panobinostat arm died from non-cancer complications compared to just 3.5% in other group, reporting symptoms including myelosuppression, hemorrhage, infection, gastrointestinal toxicity and cardiac toxicity. Panobinostat can boost progression-free survival; patients receiving the panobinostat regimen saw a delay in their disease progression for about 10.6 months versus 5.8 months in those given with bortezomib and dexamethasone alone.