Retrospective Evaluation of Thromboembolism Risk in Ovarian Cancer Patients Treated with Bevacizumab

Abstract

BackgroundBevacizumab is used in addition to standard, platinum-based chemotherapy to treat advanced-stage ovarian cancer patients. Thrombosis is a well-documented adverse effect of bevacizumab.ObjectiveThe aim of this study was to identify predictive parameters for thromboembolic events in ovarian cancer patients and to explain how bevacizumab increases the risk of these events.Patients and MethodsFifty-seven FIGO stage III ovarian cancer patients who underwent cytoreductive surgery and chemotherapy were identified and included in this retrospective study. Twenty-six patients were treated with carboplatin and paclitaxel (CP) only (control group), and 31 patients received CP with bevacizumab (study group). The two groups were compared with regard to thrombosis risk factors and laboratory parameters (total leukocytes, platelet count, hemoglobin, APTT, prothrombin time, INR, fibrinogen levels, D-dimer concentration) before treatment, after each course of chemotherapy, and during thromboembolic events.ResultsOnly patients in the group receiving bevacizumab experienced venous thromboembolism (VTE) (p=0.03, χ² test). VTE occurred on average at the 13th cycle of chemotherapy. Patients who experienced VTE had increased BMI before chemotherapy as compared to patients with no thromboembolic event (27.2 vs. 23.3, p=0.005, Mann-Whitney test). D-dimer concentration before treatment was also elevated more in patients affected by VTE (3132.5) than in the non-VTE group (956.43) (p=0.0007, Mann-Whitney test). During the first four administrations of chemotherapy in patients with future VTE, there was a reduction in D-dimer concentration and an extension of APTT. A D-Dimer level higher than 485 ng/mL prior to first chemotherapy indicates for a risk of VTE with 94% sensitivity and 36% specificity.ConclusionsAn elevated D-dimer level and high BMI before chemotherapy are risk factors for VTE in ovarian cancer patients receiving bevacizumab. Bevacizumab possibly increases the risk for VTE.

Meta-Analysis of VTE Risk: Ovarian Cancer Patients by Stage, Histology, Cytoreduction, and Ascites at Diagnosis

“…The most commonly used anticoagulation risk assessment tools for ovarian cancer patients are nonspecific or do not include important variables such as histology [ 56 – 62 ]. Most tools were created for generalized abdominal/pelvic surgery or oncology patients [ 56 – 59 , 61 ]. Risk assessment tools specific to ovarian cancer patients that have ascites at diagnosis, stage at diagnosis, and histology of tumor may be useful [ 62 , 63 ].…”

The prevalence, risk factors, and prognostic value of venous thromboembolism in ovarian cancer patients receiving chemotherapy: a systematic review and meta-analysis

“…Finally, 11 studies were included in the current meta-analysis (Fig. 1 ) [ 14 – 17 , 27 – 33 ].

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“… Greco et al, 2017 [ 32 ] Neoadjuvant chemotherapy (details were unavailable). Kuk et al, 2017 [ 33 ] The control group (26 patients) was treated with three to six cycles of standard first-line chemotherapy consisting of carboplatin (AUC 6 i.v.) and paclitaxel (175 mg/m 2 i.v.)…”

PARP-inhibitors in a non‐oncological indication as COVID-19: Are we aware about its potential role as anti-thrombotic drugs? The discussion is open

“…Noteworthy, patients under anti-PARP-1 regimens [ 18 , 19 ], particularly those with pancreatic, prostate, ovarian and breast cancers (most of them enrolled in clinical trials), might be more protected by the SARS-CoV-2 severe effects, like the thrombotic events. I underline that Bevacizumab administration was reported to be associated to venous thromboembolism in ovarian cancer patients, mostly in those with elevated D-dimer level and high BMI before chemotherapy [ 20 ]. Contrastingly, these findings were never reported for Olaparib [ 17 ].…”