Bortezomib was granted full approval as treatment for previously treated patients with multiple myeloma (MM)after publication of the initial results of the Assessment of Proteosome Inhibition for Extending Remissions (APEX) trial in 2005, which demonstrated that bortezomib improved survival in these patients compared with dexamethasone.OBJECTIVE
To assess whether, after extended follow-up, bortezomib continued to provide better survival than high-dose dexamethasone in patients with relapsed MM.DESIGN AND INTERVENTION
This randomized, phase III trial recruited patients with MM and recognizable disease after one to three previous treatments. Patients were randomized to receive either 1.3 mg/m2 bortezomib (n = 333) on days 1, 4, 8 and 11 of ight 3-week cycles and then on days 1, 8, 15 and 22 of three 5-week cycles, or 40 mg dexamethasone (n = 336) on days 1-4, 9-12, and 17-20 of four 5-week cycles, and then on days 1-5 of five 4-week cycles. Assessment of disease status and survival took place every 3 weeks for a period of 39 weeks. Follow-up took place every 6 weeks until progressive disease, and then every 3 months to document survival.OUTCOME MEASURES
Response rate and survival were the main outcome measures.RESULTS
The median follow-up time in surviving patients was 22 months, at which point 44%of patients included in the original analysis had died. In the bortezomib arm, median overall survival was 29.8 months compared with 23.7 months in the dexamethasone arm (hazard ratio 0.77; P = 0.027). The 1-year survival rates for the bortezomib group and the dexamethasone group were 80% and 67%, respectively (P = 0.001). In comparison with the initial analysis, overall response rate (complete response + partial response) in the bortezomib arm improved from 38% to 43%; complete response rate improved from 6%at initial analysis to 9%. Median time to progression, time to first response and duration of response (DOR) in the bortezomib group were unchanged from the initial analysis. Median DOR was longer in patients achieving 100% M-protein reduction (n = 40, 11.5 months) than in patients achieving less than 100% but greater than 50% reductions (n = 71, 7.6 months).There was no association between DOR and time to first response. Of the 135 patients responding to bortezomib, 54% achieved their first response after treatment cycle 2; 35% of patients achieved their best response in cycle 1 or 2.CONCLUSION
This study demonstrates that, compared with high-dose dexamethasone, bortezomib confers superior survival on previously treated patients with relapsed MM. The data support extended treatment with single-agent bortezomib beyond initial response in patients able to tolerate therapy.