Vantage 088: In Bortezomib Sensitive
Dr. Meletios Dimopoulos presented data from the randomized phase III Vantage 088 trial involving 637 patients who had progressive disease after one to three prior treatments, but were bortezomib sensitive. Patients were randomized to the same combination regimen that was used in Vantage 095, or to vorinostat 400 mg/day on days 1-14 plus placebo.
The combination of bortezomib plus vorinostat increased the primary end point of progression-free survival from 6.83 months to 7.63 months (hazard ratio, 0.774; P = .01). Although the difference reached statistical significance, the audience questioned the clinical significance of a 25-day advantage, and pointed out that this was the very first salvage line for 45% of patients in the bortezomib/vorinostat arm vs. 40% in the control arm. In addition, median overall survival was not significantly different between the bortezomib/vorinostat and control arms.
Dr. Dimopoulos responded that Vantage 088 was indeed a positive trial because one in five patients benefited from the combination. "If vorinostat is approved for the use of myeloma, it is sure that we will find better ways to use it, as is the case with bortezomib today," he said.
Using EBMT criteria, the combination of vorinostat plus bortezomib significantly improved the overall response (56% vs. 41%) and clinical benefit rates (71% vs. 53%), compared with bortezomib alone (both P less than .0001). Duration of response by EBMT criteria was similar at 8.5 months and 8.4 months, respectively, reported Dr. Dimopoulos of the department of clinical therapeutics at the National and Kapodistrian University of Athens.
Subgroup analyses revealed no significant differences between the two arms in overall response or progression-free survival based on age, type of melanoma, number of previous lines of therapy, or prior exposure to IMiDs or bortezomib.
At baseline, 46% of the 317 patients in the bortezomib/vorinostat arm and 48% of the 320 patients in the bortezomib/placebo arm were nonresponsive to their last line of therapy.
Dr. Siegel reported receiving research funding and honoraria and serving as a speaker for Millennium Pharmaceuticals and honoraria from Merck. His coauthors reported financial relationships with several firms including Millennium, Merck, and Novartis. Dr. Dimopoulos reported consultancy and honoraria from Celgene and Ortho-Biotech. His coauthors reported relationships with multiple pharmaceutical firms.