LBH589 Meets Primary End Point in Phase III PANORAMA-1 Study

LBH589, when used in combination with bortezomib and dexamethasone, improved progression-free survival among relapsed and refractory patients with multiple myeloma.

At the American Society of Clinical Oncology (ASCO) conference in Chicago, Ill., Novartis researchers presented data from the 768-patient, 215-center PANORAMA-1 (PANobinostat ORAl in Multiple Myeloma) trial showing that its investigational drug, LBH589, improved progression-free survival by a median of 4 months among patients with relapsed or refractory multiple myeloma who had received at least 1 prior therapy.^1,2

In patients who received bortezomib and dexamethasone with placebo, progression-free survival was 37% shorter than among patients receiving LBH589 with bortezomib and dexamethasone (hazard ratio = 0.63 [95% confidence interval (CI): 0.52 to 0.76]; P <.0001). These results led the FDA to grant Novartis priority review for LBH589 in May.¹

In addition, investigators reported improvements in the percentage of patients experiencing either complete response or near-complete response (28% versus 16%; P = .00006). Importantly, the efficacy of LBH589 was proven across several subgroups of patients, including older patients, patients who had received bortezomib as a prior therapy, and patients who received immunomodulatory treatment.¹

Grade-3 and -4 adverse events, including thrombocytopenia, lymphopenia, neutropenia, and diarrhea, were more common among patients in the treatment arm versus the placebo arm.¹

Mechanistically, LBH589 (also known as panobinostat), is a pan-deacetylase (pan-DAC) inhibitor. Histone deacetylases are known to play several roles in tumorigenesis, including modulation of angiogenesis, cell adhesion, cell migration, and cell differentiation.^1-4

In a press release, the Global Head of Novartis Oncology Development and Medical Affairs, Alessandro Riva, MD, stated, “LBH589 is a strong example of how our research and development strategy of targeting key pathways in novel ways can benefit patients.”

As the PANORAMA-1 trial is ongoing, data on overall survival are not yet complete. Additional data are expected later this year.^1,2

References:

• Novartis data at ASCO show LBH589 significantly improved progression-free survival in patients with multiple myeloma [press release]. http://www.novartis.com/newsroom/media-releases/en/2014/1789847.shtml. Accessed June 2014.
• ClinicalTrials.gov. Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma (PANORAMA-1). http://clinicaltrials.gov/ct2/show/NCT01023308. Accessed June 2014.
• Minucci S, Pelicci PG. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer. 2006;6(1):38-51.
• Dokmanovic M, Clarke C, Marks PA. Histone deacetylase inhibitors: overview and perspectives. Mol Cancer Res. 2007;5(10):981-989.