Objective: Advanced ovarian clear cell carcinoma (OCCC) is associated with poor outcomes owing to chemoresistance. Bevacizumab (Bev) is increasingly being used to treat advanced ovarian cancer; however, its efficacy in OCCC remains unclear. This study evaluated the treatment outcomes of frontline bevacizumab chemotherapy in patients with OCCC. Methods: This retrospective multi-institutional study included patients diagnosed with advanced OCCC at eight institutions in Japan between 2008 and 2018. Patients were categorized into pre and post-market groups based on the Bev approval dates. Progressionfree survival (PFS) and overall survival (OS) were analyzed using univariate and multivariate methods. Additionally, patients were classified into Bev-treated (Bev+) and non-Bev-treated (Bev−) groups, and their prognoses were compared. Results: A total of 96 patients were in the pre-market group and 82 in the post-market group. The post-market group had a significantly higher proportion of patients with poor performance status and patients who underwent interval debulking surgery (p<0.01 and p<0.01, respectively). Univariate analysis demonstrated a better PFS in the post-market group (p=0.041). In multivariate analysis, better PFS (hazard ratio [HR]=0.52; p=0.002) and OS (HR=0.47; p=0.002) were observed in the post-market group than in the pre-market group.Bev+ patients had significantly better PFS and OS than Bev− patients in univariate (p<0.001 and p<0.001, respectively) and multivariate analyses (PFS: HR=0.36; p<0.001 and OS:HR=0.21; p=0.001, respectively). Conclusion Incorporating Bev into frontline chemotherapy may improve outcomes in patients with advanced OCCC.

Objective: Direct oral anticoagulants (DOACs) are increasingly being used for the treatment of cancer-associated venous thromboembolism (CAT). However, there is limited evidence of the efficacy of DOACs for the treatment of gynecological CAT. Thus, this study aimed to investigate the efficacy and safety of edoxaban for the treatment of gynecological CAT using Japanese real-world data. Methods: We reviewed the medical records of patients with 371 gynecological cancer who received edoxaban or vitamin K antagonist (VKA) between January 2011 and December 2018. Results: Altogether, 211 and 160 patients were treated with edoxaban and VKA, respectively. Fourteen patients (6.8%) in the edoxaban group and 22 (13.8%) in the VKA group showed recurrence of venous thromboembolism (VTE). Cumulative VTE recurrence was not significantly different between the 2 groups (p=0.340). Adverse events occurred in 15 (7.1%) and 11 (6.9%) patients in the edoxaban and VKA groups, respectively (p=0.697). Subgroup analysis of the edoxaban and VKA groups according to different tumor types, including ovarian, endometrial, and cervical cancer, showed equivalent outcomes in terms of VTE recurrence and adverse events. Patients without pulmonary embolism (PE) were mostly omitted from initial unfractionated heparin (UFH) therapy prior to administration of edoxaban. However, this did not increase the recurrence of VTE. Conclusion This study confirmed that edoxaban is effective and safe for the treatment of gynecological CAT. This finding was consistent for different types of gynecological cancer. Additionally, initial UFH therapy prior to the administration of edoxaban may be unnecessary for patients without PE.