Bortezomib vs. dexamethasone in relapsed multiple myeloma: A phase 3 randomized study

Abstract

6511 Background: Bortezomib (Velcade, Millennium Pharmaceuticals), a novel proteasome inhibitor, is effective in refractory multiple myeloma (MM). For the APEX Study Group we present the interim results of an international, randomized phase 3 study conducted at 95 sites. Methods: Between June 2002 and Oct 2003 669 patients (pt) with relapsed MM previously treated with 1–3 prior therapies were randomized to bortezomib (Vc) (327 pts) 1.3 mg/m2 IV days 1,4,8,11 q 3 weeks for 8 cycles followed by 1.3 mg/m2 IV days 1,8,15,22 q 5weeks for 3 cycles versus dexamethasone (D) (330 pts) 40 mg po days 1–4, 9–12, 17–20 q 5 weeks for 4 cycles followed by 40mg po days 1–4 every 28 days for 3 cycles. The primary endpoint was time to progression (TTP) using EBMT criteria for progressive disease (PD). Secondary endpoints were overall survival (OS), incidence of ≥grade 3 infection and time to skeletal event (TSE). Pt progressing on D were offered Vc on a companion study. Results: Median age was 62 with no apparent differences in baseline characteristics. At the interim analysis (IA) 254 PD events had occurred. Pt receiving Vc demonstrated a highly significant benefit in TTP. Median TTP was 5.7 months (95% CI: 5.0, 7.9) on Vc and 3.6 months (95% CI: 3.2, 4.8) on D (p<0.0001, log-rank test). Overall survival was longer on Vc (p=0.038, log-rank test), with 13 deaths on Vc and 24 on D, but median survival was not reached on either arm. A trend towards a lower incidence of ≥grade 3 infections was also noted with 22 (6.7%) on Vc vs 35 (10.6%) on D (p=0.096, Fisher's exact test). No difference was noted in TSE (p=0.954, log-rank test). No other major safety differences were noted. Following the interim analysis, the Data Monitoring Committee recommended that treatment on the D arm be halted, and patients randomized to D were allowed to receive Vc. Conclusions: At the IA bortezomib was significantly more effective than dexamethasone for patients with relapsed MM. Further evaluation of survival, response duration, response rate, and safety are ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Millennium Pharmaceuticals Speaker's Bureau Millennium Pharmaceuticals Millennium Pharmaceuticals Millennium Pharmaceuticals Millennium Pharmaceuticals