Safety of direct oral anticoagulants in patients with advanced solid tumors receiving anti-VEGF agents: a retrospective study

• Published in: Supportive care in cancer 2023-01, Vol.31 (1), p.41, Article 41
• Main Authors: Boileve, Alice, Albiges, Laurence, Ducreux, Michel, Baudin, Eric, Leary, Alexandra, Besse, Benjamin, Hadoux, Julien, Malka, David, Rieutord, André, Scotté, Florian, Maulard, Amandine, Mir, Olivier
• Format: Article
• Language: English
• Subjects: Administration, Oral; Aged; Antibodies; Anticoagulants; Anticoagulants (Medicine); Anticoagulants - adverse effects; Antimitotic agents; Antineoplastic agents; Bevacizumab - adverse effects; Cancer patients; Care and treatment; Dabigatran - adverse effects; Female; Hemorrhage - chemically induced; Hemorrhage - epidemiology; Humans; Inhibitor drugs; Kidney cancer; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Metastasis; Monoclonal antibodies; Neoplasms - drug therapy; Nursing; Nursing Research; Oncology; Oral administration; Original Article; Pain Medicine; Patient safety; Patients; Pulmonary Embolism; Pulmonary embolisms; Rehabilitation Medicine; Retrospective Studies; Rivaroxaban - adverse effects; Safety and security measures; Sarcoma; Targeted cancer therapy; Thromboembolism; Tumors; Vascular endothelial growth factor; Viral antibodies
• ISSN: 0941-4355; 1433-7339; 1433-7339
• DOI: 10.1007/s00520-022-07533-1

Purpose Kinase inhibitors (KI) and antibodies targeting the VEGF pathway are approved in a broad spectrum of cancers and associated with an increased risk of bleeding and thromboembolic events (TE). The use of direct oral anticoagulants (DOACs) apixaban and rivaroxaban is increasing in cancer patients, but limited data are available for patients receiving anti-VEGF agents. Methods To assess safety of DOAC with concomitant anti-VEGF agents, a retrospective chart review of all patients receiving concomitantly DOAC and anti-VEGF agents was performed from 2013 to 2020 in our center. Data on demographics, safety, and time on treatment were collected. Main outcome was safety (bleeding and thromboembolic events). Results Of 92 patients (median age 66 years (IQR: 59–72)), 40 were treated with KI and 52 with bevacizumab. The most frequent primary tumor sites were colon/rectum (24%), kidney (21%), ovary (13%), lung (11%), soft tissue sarcoma (10%), and thyroid (9%); 2% had brain metastases. Apixaban 5 mg bid ( n  = 41) or rivaroxaban 20 mg daily ( n  = 51) were given for TE (65%), atrial fibrillation (32%), or other indications (3%). The median duration of concomitant treatment was 4.8 months (95%CI: 0.7–50.0) with bevacizumab and 11.7 months (95%CI: 0.1–53.8) with KI. Grade ≥ 3 bleeding events occurred in 5 patients (5%): 4 patients receiving bevacizumab (one grade 5 upper digestive tract bleeding and three grade 3 rectal or vaginal hemorrhages) and 1 patient under cabozantinib for kidney cancer with endobronchial metastasis (grade 3 hemoptysis). Grade ≥ 3 TE occurred in 8 patients (9%): 7 patients receiving bevacizumab (including one grade 5 pulmonary embolism), and one patient receiving sunitinib (grade 3 pulmonary embolism). Median time-to-event (bleeding or thrombotic event) was not reached (NR) (95%CI: 76.9-NR) for KI and 86.9 months (95%CI: 42.9–148.0) for bevacizumab. Conclusions and relevance In our experience, the use of DOAC was safe in selected patients treated with KI, but unclear with bevacizumab. More data are needed to endorse guidelines in this specific group of patients.