Bortezomib and Vorinostat Safe and Effective in Phase 3 Trial

San Diego—Patients with relapsed and refractory multiple myeloma who took a combination of bortezomib and vorinostat had a significantly longer progression-free survival and time to progression compared with a group that took bortezomib alone, according to a global, randomized, double-blind, phase 3 study presented at the ASH meeting. The combination of bortezomib and vorinostat was also well tolerated. Meletios Dimopoulos, MD, professor in the department of therapeutics at the University of Athens, Greece, discussed the results during an oral abstract session at the meeting. Dr. Dimopoulos said nearly all patients with multiple myeloma have relapses and become refractory to treatment, although earlier phase trials indicated that bortezomib plus vorinostat was safe and effective. The VANTAGE 088 (Vorinostat Clinical Trials in Hematologic and Solid Malignancies) trial enrolled 637 patients from 174 centers in 33 countries who had received 1 to 3 prior treatment regimens, were sensitive to bortezomib, and whose disease had progressed after the most recent treatment. As part of a 21-day treatment cycle, patients received 1.3 mg/m2 of bortezomib intravenously on days 1, 4, 8, and 11 in combination with 400 mg of vorinostat or placebo once daily on days 1 through 14. There were 317 patients in the bortezomib plus vorinostat group and 320 patients in the bortezomib plus placebo group. Baseline characteristics for the groups were similar. Approximately 60% of patients were males, the median age was approximately 62 years, and the median time since initial treatment was approximately 3 years. Nearly 60% of patients had taken ≥2 prior lines of therapy before entering the trial, and nearly half had been nonresponsive to their last line of therapy. The median progression-free survival was 7.63 months in the bortezomib plus vorinostat group compared with 6.83 months in the bortezomib plus placebo group (hazard ratio, 0.774; 95% confidence interval, 0.64-0.94; P=.01). A trend in favor of overall survival was observed in the bortezomib plus vorinostat arm, but the difference was not statistically significant. The authors also utilized the European Group for Blood and Bone Marrow Transplant response assessment to measure the response rates for both groups. The bortezomib plus vorinostat group had a clinical benefit rate of 71% compared with 54% for the bortezomib plus placebo group (P<.0001). The overall response rate was 56% in the bortezomib plus vorinostat group and 41% in the bortezomib plus placebo group (P<.0001). Patients in the bortezomib plus vorinostat group took an average of 8.2 cycles of treatment, 50% had vorinostat dose reductions, and 63% had their bortezomib dose reduced, with a median time to the first dose reduction of 92 days. Patients in the bortezomib plus placebo group took an average of 7.6 cycles of treatment, 25% had vorinostat dose reductions, and 49% had their bortezomib dose reduced, with a median time to the first dose reduction of 124 days. The rates of serious adverse events were similar (41% in the bortezomib plus vorinostat group and 43% in the bortezomib plus placebo group). Also, 21% of patients in the bortezomib plus vorinostat group and 22% in the bortezomib plus placebo group discontinued the study because of an adverse event. Three patients in the bortezomib plus vorinostat group and 5 patients in the bortezomib plus placebo group died during the treatment or follow-up period, with 1 death in each group attributable to a drug-related adverse event.