by Dr. C.H.Weaver M.D. updated 3/2019
The US Food and Drug Administration (FDA) approved Farydak® (panobinostat) in combination with Velcade® and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior regimens, including Velcade® and an immunomodulatory (IMiD) agent.(1,2)
The FDA approval was partially based on the results of the phase III PANORAMA1 trial reported in late 2014 in The Lancet Oncology. In this study San-Miguel and colleagues found that adding the pan-deacetylase inhibitor Farydak® to Velcade® and dexamethasone improved progression-free survival in patients with relapsed or relapsed and refractory multiple myeloma.
Farydak® is a drug that belongs to a class of drugs called histone deacetylase (HDAC) inhibitors, which work by increasing the production of proteins that slow cell division and cause cell death. It is being studied in myeloma as well as other blood cancers and solid tumors. The HDAC inhibitors have demonstrated improved anti-cancer activity if they are used in combination with a class of agents called proteasome inhibitors, such as Velcade (bortezomib) and Kyrpolis® (carfilzomib).
In the PANORAMA1 clinical trial 768 patients from 215 centers in 34 countries who had relapsed or relapsed and refractory multiple myeloma were treated with either Farydak®, Velcade, and dexamethasone or a standard treatment regimen of Velcade, and dexamethasone and directly compared.
Farydak® treated patients experienced an improvement in time to cancer progression from 8 to 12 months with over twice as many patients surviving 2 years from treatment.
Patients in the Farydak® treatment group were more likely to experience diarrhea and low platelet and white blood cell counts often resulting in the discontinuation of treatment.
Although Farydak® was associated with more toxicity especially to the bone marrow, its addition to a Velcade treatment regimen clearly improved time to cancer progression.(1)
Subgroup analysis of patients treated on the PANORAMA 1 clinical trial further revealed the following.(2)
- Among patients who had received therapy with an IMiD prior to the trial, median PFS was 12.3 months for those treated with the addition of panobinostat to bortezomib/dexamethasone, compared with 7.4 months for those treated with placebo/bortezomib/dexamethasone.
- Among patients who had received therapy prior to the trial with bortezomib plus an IMiD, median PFS was 10.6 months for those treated with the addition of panobinostat to bortezomib/dexamethasone, compared with 5.8 months for those treated with placebo/bortezomib/dexamethasone.
- Among patients who had received therapy prior to the trial with two or more regimens, including an IMiD and bortezomib, median PFS was 12.5 months for those treated with the addition of panobinostat to bortezomib/dexamethasone, compared with 4.7 months for those treated with placebo/bortezomib/dexamethasone.
- Severe side effects were similar regardless of the number of therapies patients had received prior to the trial.
- Richardson PG, Schlossman RL, Alsina M, et al. PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma. Blood. 2013; 122(14):2331-2337.
- San-Migule J, Hungira V, Yoon S-S, et al. Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial. The Lancet Oncology, Volume 15, Issue 11, Pages 1195 – 1206, October 2014.
- Richardson P, Hungria V, Yoon S-S, et al. Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma: outcomes by prior treatment. Blood. 2016;127(6): 713-721. DOI: http://dx.doi.org/10.1182/blood-2015-09-665018. Available at: http://www.bloodjournal.org/content/127/6/713?sso-checked=true. Accessed February 17, 2016