Efficacy and Safety of Once-Weekly versus Twice-Weekly Bortezomib in Patients with Hematologic Malignancies: A Meta-analysis with Trial Sequential Analysis

Abstract

Study objective: To compare the efficacy and safety of once-weekly and twice-weekly bortezomib therapy in patients with hematologic malignancies.

Design: Meta-analysis of 13 clinical or randomized controlled trials, with trial sequential analysis (TSA).

Patients: A total of 1567 patients with hematologic malignancies who received either once-weekly or twice-weekly bortezomib therapy.

Measurements and main results: We conducted a comprehensive literature search of the PubMed, EMBASE, and Cochrane Library databases. A meta-analysis was conducted to calculate the pooled effect size; TSA was performed to assess the reliability of the pooled results. The pooled risk ratio (RR) for the overall response rate (ORR) was 1.00 (95% confidence interval [CI] 0.77-1.29, p=0.99), indicating no significant differences between patients who received once-weekly bortezomib and those who received twice-weekly bortezomib. TSA showed that the cumulative Z-curve of the ORR entered the futility area, implying that reliable evidence was obtained for this pooled result. The pooled RR for any grade of peripheral neuropathy was 0.48 (95% CI 0.26-0.88, p=0.02); however, the TSA plot revealed that there was insufficient evidence for this result. The pooled RR for peripheral neuropathy grade 3 or higher was 0.21 (95% CI 0.13-0.34, p<0.00001), and reliable evidence was obtained according to TSA. Regarding the other toxicities, including anemia, thrombocytopenia, neutropenia, infection, diarrhea, constipation, nausea, vomiting, and fatigue, we did not find any significant differences between patients who received once-weekly bortezomib and those who received twice-weekly bortezomib.

Conclusion: Compared with twice-weekly bortezomib, once-weekly bortezomib had a comparable ORR and a probable lower incidence of peripheral neuropathy. More clinical trials are needed to draw a conclusion regarding the difference in peripheral neuropathy between the two groups because of the insufficient evidence detected by TSA and the inconsistent results among subgroups.

Keywords: bortezomib; hematologic malignancies; meta-analysis; once-weekly; trial sequential analysis; twice-weekly.