Indirect comparison of azacitidine and decitabine for the therapy of elderly patients with acute myeloid leukemia: a systematic review and network meta-analysis

Background The DNA hypomethylating agents (HMAs) decitabine and azacitidine have been widely used in the management of elderly patients with acute myeloid leukemia (AML). However, no direct clinical trials have been carried out to compare the two agents. A systematic review and network meta-analysis were performed to indirectly compare the efficacy and safety of decitabine and azacitidine in elderly AML patients. Methods We systematically searched PubMed, Medline, Web of Science, Embase and Cochrane Library through May 14, 2019. Randomized controlled trials on elderly AML patients comparing the efficacy and safety between decitabine and azacitidine, or comparing one of HMAs to standard supportive care or placebo were selected. The major outcomes of interest were performed with methods of adjusted indirect comparison and the fixed effect model. Results Only three RCTs including a total number of 1086 patients were identified. Direct comparisons showed that azacitidine significantly reduced mortality (RR = 0.90, 95% CI 0.83-0.97) while decitabine was not significantly associated with lower mortality (RR = 0.97, 95% CI 0.92-1.02) compared to the conventional care regimen (CCR). In addition, for the indirect method, azacitidine significantly reduced mortality compared to decitabine (RR = 0.83 95% CI 0.77-0.90) and was more likely to improve complete response (CR) (RR = 1.66, 95% CI 1.17-2.35, low-certainty evidence). No statistical significance was found for the other studied outcomes. Conclusions Compared to CCR, decitabine and azacitidine can promote studied outcomes in elderly AML patients. Indirect evidence with low certainty was used to compare these two agents. The superiority of either agent cannot be confirmed, and head-to-head clinical trials are still required.