Objective: DUO-E/GOG-3041/ENGOT-EN10 (NCT04269200) demonstrated statistically significant and clinically meaningful progression-free survival (PFS) improvement with durvalumab plus carboplatin/paclitaxel, followed by durvalumab with or without olaparib, vs. carboplatin/paclitaxel alone (intention-to-treat [ITT] population) in patients with newly diagnosed advanced or recurrent endometrial cancer. We evaluated efficacy and safety in the Japan subset of DUO-E. Methods: Patients with newly diagnosed International Federation of Gynecology and Obstetrics stage III/IV or recurrent endometrial cancer were randomized 1:1:1 to control arm (carboplatin/paclitaxel + durvalumab placebo [6 cycles] followed by durvalumab placebo + olaparib placebo), durvalumab arm (carboplatin/paclitaxel + durvalumab [1,120 mg every 3 weeks] [6 cycles] followed by durvalumab [1,500 mg every 4 weeks] + olaparib placebo), or durvalumab + olaparib arm (carboplatin/paclitaxel + durvalumab [6 cycles] followed by durvalumab + olaparib [300 mg twice a day]). Dual primary endpoints were investigatorassessed PFS for durvalumab and durvalumab + olaparib arms vs. control. This prespecified exploratory analysis evaluated PFS and safety in the Japan subset. Results: In the Japan subset (n=88) PFS favored durvalumab (hazard ratio=0.61, 95% confidence interval [CI]=0.32–1.12) and durvalumab + olaparib (0.44, 95% CI=0.22–0.85) vs. control; median PFS was 9.9 and 15.1 vs. 9.5 months, and the 18-month PFS rate was 37.0% and 42.1% vs. 22.2%, respectively. The safety profile in the Japan subset was generally consistent with the full safety analysis set and the established profiles of the individual agents. Conclusion Efficacy and safety in the Japan subset were generally consistent with outcomes in the DUO-E ITT population. This Japanese subset analysis of DUO-E supports carboplatin/ paclitaxel + durvalumab followed by durvalumab with or without olaparib as new treatment options in patients with advanced or recurrent endometrial cancer and is the first to report on these regimens in Japanese patients alone.

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: This study compared the effectiveness, safety, and tolerability of dose-dense paclitaxel and carboplatin plus bevacizumab (ddTC+Bev) with ddTC for advanced ovarian cancer. Methods: We retrospectively analyzed the clinical records of 134 patients who received ddTC+Bev or ddTC as first-line chemotherapy for stage III–IV ovarian cancer. Progressionfree survival as primary endpoint of this study was compared using the log-rank test. Cox proportional hazards model and propensity score matching (PSM) were used to analyze prognostic factors, and the frequency of adverse events was examined using the χ 2 test. Results: We categorized 134 patients in the ddTC+Bev (n=57) and ddTC (n=77) groups who started treatment at four related institutions from November 2013 to December 2017.No patients used poly (ADP-ribose) polymerase inhibitors as the first line maintenance therapy. The progression-free survival (PFS) of the ddTC+Bev group had a significantly better prognosis than that of the ddTC group (hazard ratio [HR]=0.50; 95% confidence interval [CI]=0.32–0.79; p<0.003). Multivariate analysis showed that ddTC+Bev regimen was a prognostic factor. However, intergroup comparison using PSM revealed that the PFS of the ddTC+Bev group had a nonsignificantly better prognosis than that of the ddTC group (HR=0.70; 95% CI=0.41–1.20; p=0.189). Few adverse events above G3 were noted for ddTC+Bev, which were sufficiently tolerable. Conclusion This study could not demonstrate that adding Bev to ddTC improves prognosis.Further studies with more cases are warranted.

Objective: This study compared the effectiveness, safety, and tolerability of dose-dense paclitaxel and carboplatin plus bevacizumab (ddTC+Bev) with ddTC for advanced ovarian cancer. Methods: We retrospectively analyzed the clinical records of 134 patients who received ddTC+Bev or ddTC as first-line chemotherapy for stage III–IV ovarian cancer. Progressionfree survival as primary endpoint of this study was compared using the log-rank test. Cox proportional hazards model and propensity score matching (PSM) were used to analyze prognostic factors, and the frequency of adverse events was examined using the χ 2 test. Results: We categorized 134 patients in the ddTC+Bev (n=57) and ddTC (n=77) groups who started treatment at four related institutions from November 2013 to December 2017.No patients used poly (ADP-ribose) polymerase inhibitors as the first line maintenance therapy. The progression-free survival (PFS) of the ddTC+Bev group had a significantly better prognosis than that of the ddTC group (hazard ratio [HR]=0.50; 95% confidence interval [CI]=0.32–0.79; p<0.003). Multivariate analysis showed that ddTC+Bev regimen was a prognostic factor. However, intergroup comparison using PSM revealed that the PFS of the ddTC+Bev group had a nonsignificantly better prognosis than that of the ddTC group (HR=0.70; 95% CI=0.41–1.20; p=0.189). Few adverse events above G3 were noted for ddTC+Bev, which were sufficiently tolerable. Conclusion This study could not demonstrate that adding Bev to ddTC improves prognosis.Further studies with more cases are warranted.

Objective: This study compared the effectiveness, safety, and tolerability of dose-dense paclitaxel and carboplatin plus bevacizumab (ddTC+Bev) with ddTC for advanced ovarian cancer. Methods: We retrospectively analyzed the clinical records of 134 patients who received ddTC+Bev or ddTC as first-line chemotherapy for stage III–IV ovarian cancer. Progressionfree survival as primary endpoint of this study was compared using the log-rank test. Cox proportional hazards model and propensity score matching (PSM) were used to analyze prognostic factors, and the frequency of adverse events was examined using the χ 2 test. Results: We categorized 134 patients in the ddTC+Bev (n=57) and ddTC (n=77) groups who started treatment at four related institutions from November 2013 to December 2017.No patients used poly (ADP-ribose) polymerase inhibitors as the first line maintenance therapy. The progression-free survival (PFS) of the ddTC+Bev group had a significantly better prognosis than that of the ddTC group (hazard ratio [HR]=0.50; 95% confidence interval [CI]=0.32–0.79; p<0.003). Multivariate analysis showed that ddTC+Bev regimen was a prognostic factor. However, intergroup comparison using PSM revealed that the PFS of the ddTC+Bev group had a nonsignificantly better prognosis than that of the ddTC group (HR=0.70; 95% CI=0.41–1.20; p=0.189). Few adverse events above G3 were noted for ddTC+Bev, which were sufficiently tolerable. Conclusion This study could not demonstrate that adding Bev to ddTC improves prognosis.Further studies with more cases are warranted.

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.

OBJECTIVE: Since there have been few large series studies to date, we investigated the relationship between Trousseau's syndrome associated with cerebral infarction and its clinical associations with ovarian cancer. METHODS: In this study, we investigated the association between cerebral infarction onset and ovarian cancer. Eight-hundred twenty-seven consecutive ovarian cancer patients from 4 affiliated academic institutions were included in the study over a 12 years period. All patients were histopathologically diagnosed as epithelial ovarian cancer and were analyzed retrospectively. RESULTS: The 27 patients (3.2%) presented with cerebral infarction during the study period, 14 patients onset prior to treatment (1.7%), and 13 patients onset after start of initial treatment (1.5%). Univariate analysis and multivariate analysis was performed for onset of Trousseau's syndrome and various clinical and pathological parameters. There was no statistical significance between the occurrence of Trousseau's syndrome with age or International Federation of Gynecology and Obstetrics (FIGO) stage; however, univariate analysis and multivariate analysis demonstrated a statistically significant association between clear cell carcinoma (CCC) and non-CCC histology. CONCLUSION: Thus, our results demonstrate that Trousseau's syndrome with cerebral infarction occurred with greater incidence among CCC cases compared to non-CCC cases.
Cerebral Infarction* ; Gynecology ; Humans ; Incidence ; Multivariate Analysis ; Obstetrics ; Ovarian Neoplasms* ; Retrospective Studies ; Thromboembolism

OBJECTIVE: The aim of the study is to investigate recurrence of stage I epithelial ovarian cancer. METHODS: Six hundred two patients diagnosed with stage I epithelial ovarian cancer at 4 hospitals between 2000 and 2013 were retrospectively analyzed. Age, surgical procedure, substage, histologic type, adjuvant chemotherapy, recurrence, initial recurrence site (peritoneal dissemination [P], hematogenous recurrence [H], lymphogenous recurrence [L], and others [O]), and frequency of recurrence at each site were investigated retrospectively. RESULTS: Median age was 54 years and median follow-up was 60 months. The stage was IA in 180 cases (30%), IB in 8 (1%), IC1 in 247 (41%), IC2 in 63 (10%), and IC3 in 104 (17%). Systematic lymph node dissection including both pelvic and para-aortic lymph nodes was performed in 224 patients (37%), and 412 patients (68%) received adjuvant chemotherapy. Recurrence occurred in 70 patients (11.6%). The median time to recurrence was 18 months, and the stage was IA in 13 (19%), IB in 1 (1%), IC1 in 24 (34%), IC2 in 9 (13%), and IC3 in 23 (33%) cases. The numbers of recurrence at the P, H, L, and O sites, including overlapping cases, were 49 (70%), 18 (26%), 9 (13%), and 6 (9%), respectively, and recurrence by peritoneal dissemination in the pelvis occurred in 43 cases (61%). CONCLUSION: Recurrence of stage I epithelial ovarian cancer by peritoneal dissemination was frequent, especially in the pelvis. There is a need to elucidate the pathogenesis of peritoneal recurrence and to prepare a treatment strategy to prevent pelvic peritoneal recurrence.
Chemotherapy, Adjuvant ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Lymph Nodes ; Neoplasm Metastasis ; Neoplasm Seeding ; Ovarian Neoplasms* ; Pelvis ; Recurrence* ; Retrospective Studies*