Net Clinical Benefit of Edoxaban for 12 versus 3 Months in Cancer-associated Isolated Distal Deep Vein Thrombosis: ONCO DVT study

Background The ONCO DVT (Edoxaban for 12 Months Versus 3 Months in Patients With Cancer With Isolated Distal Deep Vein Thrombosis) study has revealed the superiority of a 12-month versus 3-month edoxaban treatment in terms of fewer thrombotic events for cancer-associated isolated distal deep vein thrombosis; however, concern for increased bleeding with longer anticoagulation remains. Methods In this post-hoc analysis of the ONCO DVT study, we compared 12-month and 3-month edoxaban treatments in terms of the net adverse clinical events (NACE) as a composite endpoint of the primary endpoint (symptomatic recurrent VTE and VTE-related death at 12 months) and major secondary endpoint (major bleeding at 12-months) of the ONCO DVT study. The net clinical benefit of a 12-month over 3-month treatment was defined as the sum of the differences in the incidence of thrombotic and bleeding events between the 3-month and 12-month treatments. The weight of bleeding events was set at 1.0, and we assessed the changes in the net clinical benefit with weights of bleeding events set at 0.5 and 2.0. Results With a weight of bleeding events of 1.0, NACE occurred in 30 of 296 patients (10.1%) in the 12-month edoxaban group and in 42 of 305 patients (13.8%) in the 3-month edoxaban group. The net clinical benefit was 3.6% (95% CI, -1.5% to 8.8%). There was a significant treatment-by-subgroup interaction between the thrombocytopenia or cancer metastasis subgroup factors and the effect of the 12-month relative to the 3-month treatment for NACE. As the weights of bleeding events changed from 0.5 to 2.0, the net clinical benefit in the 12-month edoxaban group as compared to the 3-month edoxaban group became attenuated from 4.8% (95% CI, 0.5% to 9.0%) to 0.7% (95% CI, -5.7% to 7.1%). Conclusions The net clinical benefit of the 12-month over 3-month edoxaban treatment was not significant; however, the 12-month treatment had a numerically lower incidence of NACE than the 3-month treatment. Clinical Trial Registration ClinicalTrials.gov, [NCT03895502][1]. What is new? What are the clinical implications? ### Competing Interest Statement Dr. Nishimoto received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo. Dr. Yamashita received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo, and grant support from Bayer Healthcare and Daiichi-Sankyo. Dr. Morimoto reports lecturer's fees from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Pfizer and Tsumura; manuscript fees from Bristol-Myers Squibb and Pfizer; advisory board for Novartis and Teijin. Dr. Ogihara received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo, and research funds from Bayer Healthcare and Daiichi-Sankyo. Dr. Dohi received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo, and research funds from Daiichi-Sankyo. Dr. Ikeda N. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, and Daiichi-Sankyo. Dr. Tsubata received lecture fees from AstraZeneca, Chugai Pharmaceutical, Bristol-Myers Squibb, Kyowa Kirin, Pfizer, Taiho Pharmaceutical, Takeda Pharmaceutical and Daiichi-Sankyo, and grant support from Daiichi-Sankyo, AstraZeneca and OnoPharmaceutical. Dr. Ikeda S. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb and Daiichi-Sankyo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. ### Clinical Trial ClinicalTrials.gov, [NCT03895502][1]. ### Funding Statement Funding was provided by Daiichi Sankyo Co., Ltd., which had no role in the study design, data collection, analysis, interpretation, or writing of the report. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The trial was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Kyoto University Institutional Review Board, along with the institutional review boards of all participating institutions. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data, analytic methods, and study materials will not be made available to other researchers for purposes of reproducing the results or replicating the procedure. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03895502&atom=%2Fmedrxiv%2Fearly%2F2024%2F02%2F29%2F2024.02.27.24303473.atom