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Panorama 1: A randomized, double-blind, phase 3 study of panobinostat or placebo plus bortezomib and dexamethasone in relapsed or relapsed and refractory multiple myeloma.
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: Panobinostat (PAN) is a potent pan-deacetylase inhibitor that demonstrates synergistic antimyeloma activity when combined with bortezomib (BTZ) + dexamethasone (Dex). Early studies demonstrated durable responses in patients (pts) with relapsed (Rel) and relapsed/refractory (RR) multiple myeloma (MM) treated with PAN + BTZ + Dex. This initiated the PANORAMA 1 study, presented herein. Methods: Eligible pts had Rel or RR (excluding BTZ- and primary-ref MM) following 1-3 prior regimens. Pts received oral PAN (20 mg) or placebo (pbo) 3 ×/wk + IV BTZ (1.3 mg/m2; D 1, 4, 8, 11) during wks 1-2 with oral Dex (20 mg) on the days of and after BTZ in treatment phase (TP) 1, eight 3 wk cycles. Pts demonstrating benefit could proceed to TP2, with PAN dosing maintained and BTZ/Dex less frequent. The primary endpoint was progression free survival (PFS) with response assessed by modified EBMT criteria. Other endpoints included overall survival (OS), overall response rate (ORR), near complete/complete response (nCR/CR) rate, duration of response (DOR), and safety. PFS/ORR was confirmed by an independent review committee. Results: A total of 768 pts (PAN + BTZ + Dex [n = 387]; pbo + BTZ + Dex [n = 381]) were randomized. Median age was 63 y (42% ≥ 65 y) and 48% received ≥ 2 prior regimens. Prior therapies included BTZ (43%), thalidomide (51%), lenalidomide (20%), and 25% received both prior BTZ + IMiDs. The primary endpoint was met with median PFS of 12 mo vs 8.1 mo (P < .0001; HR 0.63, 95% CI [0.52, 0.76]) for pts treated on the PAN vs pbo arm. In the PAN and pbo arms, ORR was 61% vs 55% and nCR/CR rate was 28% vs 16%, with DOR of 13.1 mo vs 10.9 mo, respectively. OS data is not mature. Adverse events (AEs) led to discontinuation in 36% in the PAN arm and 20% in the pbo arm. Common grade 3/4 lab abnormalities and AEs (regardless of study drug relationship) in the PAN vs pbo arms included thrombocytopenia (67% vs 31%), neutropenia (35% vs 11%), and diarrhea (26% vs 8%); these were generally manageable with dose reduction/supportive care. On-treatment deaths occurred in 8% and 5%, respectively. Conclusions: PAN + BTZ/Dex significantly improves PFS in pts with Rel or RR MM, with manageable toxicity. Clinical trial information: NCT01023308.
Abstracts by Paul G. Richardson:
Analysis of outcomes based on response for patients with relapsed or relapsed and refractory multiple myeloma in the phase 3 PANORAMA 1 study.Meeting: 2015 ASCO Annual Meeting | Abstract No: 8575
ELOQUENT-2: A phase III, randomized, open-label study of lenalidomide (Len)/dexamethasone (dex) with/without elotuzumab (Elo) in patients (pts) with relapsed/refractory multiple myeloma (RRMM).Meeting: 2015 ASCO Annual Meeting | Abstract No: 8508
MM-007: A phase 3 trial comparing the efficacy and safety of pomalidomide (POM), bortezomib (BORT), and low-dose dexamethasone (LoDEX [PVD]) versus BORT and LoDEX (VD) in subjects with relapsed or refractory multiple myeloma (RRMM).Meeting: 2015 ASCO Annual Meeting | Abstract No: TPS8610