Panobinostat Combination Therapy in Multiple Myeloma: Interim Results from PANORAMA

Adding panobinostat to a combination treatment of bortezomib and dexamethasone in heavily pretreated patients boosts progression-free survival, but overall survival data are not yet mature.

In a phase III trial published in the journal Lancet Oncology on September 18, 2014, researchers San-Miguel et al investigated the potential of combination therapy with panobinostat, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma.¹

Panobinostat, which is an oral pan-deacetylase inhibitor, was administered with background therapy over a 21-day cycle in which patients with relapsed myeloma received¹:

• Panobinostat 20 mg daily (or placebo) on days 1, 3, 4, 8, 10, and 12.
• Bortezomib infusions at a dosage of 1.3 mg/m² per infusion on days 1, 4, 8, and
• Dexamethasone 20 mg daily on days 1, 2, 4, 5, 8, 9, 11, and 12.

Investigators analyzed the primary end point of progression-free survival (PFS) in an intent-to-treat analysis over a median follow up duration of 6.47 months in patients receiving panobinostat (n = 387), and a median follow up duration of 5.59 months in patients receiving placebo (n = 381).¹

Mean PFS was significantly longer in patients receiving panobinostat (11.99 months versus 8.08 months; P <.0001). This improvement in PFS equates to a 47% reduction in the risk of progression with the addition of panobinostat to the therapeutic regimen.¹

Available overall survival (OS) data show a trend toward a benefit with panobinostat (33.64 months median OS with panobinostat vs 26.87 months median OS with placebo; P = .26). Importantly, however, many patients enrolled in the trial are still alive, and survival rates will not be adequately addressed until a future date.¹

In a press release, lead author of the 215-site clinical trial Jesus San-Miguel, MD, stated, “The PANORAMA-1 study is the first Phase III trial to show the superiority of LBH589 plus bortezomib and dexamethasone over one of the standard two-drug regimens for patients with relapsing and/or refractory multiple myeloma.”

Global regulatory submissions are underway, along with FDA and EMA regulatory submissions.²

Serious adverse events, including lymphopenia, diarrhea, asthenia/fatigue, and peripheral neuropathy, occurred in 60% of patients receiving panobinostat versus 42% of patients receiving placebo. Further research will determine whether panobinostat affects overall survival and whether the tradeoff of clinical benefits and adverse events justify approval of the treatment for patients with relapsed multiple myeloma.^1,2

Reference:

• San-Miguel JF, Hungria VT, Yoon SS, 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. Lancet Oncol. 2014.
• Novartis. Novartis data in The Lancet Oncology show LBH589 offers 4-month increase in median PFS for patients with multiple myeloma. http://www.novartis.com/newsroom/media-releases/en/2014/1856852.shtml. Accessed September 23, 2014.