Treatment of cancer associated thrombosis: A living interactive systematic review and bayesian network meta-analysis.
Authors: Sipra Qurat Ul Ain Riaz , Riaz Irbaz Bin , Naqvi Syed Arsalan Ahmed , He Huan , Liu Hongfang , Bryce Alan Haruo , Murad M. Hassan , McBane Robert 
Published: June 2022

e24070 Background: We have maintained a living interactive systematic review (LISR) on the treatment of CAT ( CAT LISR ). Recent publications of CASTA-DIVA and CANVAS trials prompted this report of updated analysis. Methods: The approach to creating LISRs has been previously published and is available on our website. ( LIvE synthesis framework ). Patient important outcomes included venous thromboembolism (VTE) recurrence, major bleeding (MB), clinically relevant non-major bleeding (CRNMB), net clinical benefit (NCB) and all-cause mortality. Mantel-Haenszel method was used to pool treatment effect estimates. A Paul-Mendel random-effects meta-analysis was conducted to compare DOACs with LMWH. Mixed-treatment comparisons were computed using fixed-effect model within a Bayesian framework owing to a sparse and open network. Effect estimates were expressed as odds ratio (OR) with 95% confidence intervals (CI). Surface under the cumulative ranking curve (SUCRA) was used to assess relative treatment rankings. Results: This systematic review currently includes six RCTs with a total of 3690 patients and four unique treatment choices. Apixaban was assessed in two trials (ADAM-VTE, CARAVAGGIO), rivaroxaban in two (SELECT-D, CASTA-DIVA) and edoxaban in one (HOKUSAI-VTE). CANVAS trial reported efficacy of DOACs as a class and hence, was only included in direct comparisons with LMWH. Direct comparisons showed that DOACs as a class significantly decreased the odds of VTE recurrence (OR 0.63, 95% CI: 0.49-0.82) without significantly increasing major bleeding (OR 1.23, 95% CI: 0.84-1.79) when compared to LMWH. However, higher odds of CRNMB (OR 1.65, 95% CI: 1.18-2.31) was observed with DOACs when compared to LMWH. Mortality rates were not different between the two groups (OR: 1.03, 95% CI: 0.87-1.21). Mixed treatment comparisons showed decreased VTE recurrences with rivaroxaban (rank 1; OR 0.49, 95% CI: 0.23-0.99) and apixaban (rank 2; OR 0.58, 95% CI: 0.36-0.90) relative to LMWH (rank 4). No significant differences were observed between edoxaban (rank 3) and LMWH in terms of VTE risk reduction. Edoxaban (rank 4) increased the risk of major bleeding (OR 1.77, 95% CI: 1.05-3.15) compared to LMWH (rank 2); there were no significant differences among rivaroxaban (rank 3) apixaban (rank 1), and LMWH. Rivaroxaban (rank 4; OR 3.16; 95% CI: 1.61-6.68) and apixaban (rank 3; OR 1.51, 95% CI: 1.01-2.28) increased the risk of CRNMB compared to LMWH (rank 1). Significant net clinical benefit was observed with apixaban (rank 1; OR 0.66; 95% CI: 0.46-0.94) when compared to LMWH (rank 4). No significant differences were observed among other mixed treatment comparisons. Conclusions: Patients treated with DOACs have 31 fewer VTE events per 1000 CAT patients compared to LMWH. Amongst DOACs, apixaban offers the greatest net clinical benefit with 39 fewer VTE and MB events per 1000 patients compared to LMWH.