Effects of concomitant administration of anticancer agents and apixaban or dalteparin on recurrence and bleeding in patients with cancer-associated venous thromboembolism.

BACKGROUND

Whether concomitant administration of anticancer agents influences the efficacy and safety of oral anticoagulants in patients treated for cancer-associated venous thromboembolism (VTE) is undefined. The pharmacological interaction between anticancer agents and direct oral anticoagulants is perceived as a concern.

METHODS

We evaluated the effects of concomitant administration of anticancer agents on recurrent VTE, major bleeding and death in patients with cancer-associated VTE randomised to receive apixaban or dalteparin in the Caravaggio study.

RESULTS

Anticancer agents were concomitantly given to 336 patients (58.3%) treated with apixaban and to 332 patients (57.3%) treated with dalteparin. In patients treated with apixaban, recurrent VTE occurred in 20 (6.0%) and 12 (5.0%) among patients treated or not treated with anticancer agents, respectively (hazard ratio [HR] = 1.14; 0.55-2.38); major bleeding occurred in 12 (3.6%) and 10 (4.2%) patients , respectively (HR = 0.79; 0.34-1.82), and death occurred in 74 (22.0%) and 61 (25.4%) patients , respectively (HR = 0.71; 0.51-1.00). In patients treated with dalteparin, recurrent VTE occurred in 24 (7.2%) and 22 (8.9%) among patients treated or not treated with anticancer agents, respectively (HR = 0.71; 0.40-1.28); major bleeding occurred in 16 (4.8%) and 7 (2.8%) patients, respectively (HR = 1.78; 0.66-4.79), and death occurred in 87 (26.2%) and 66 (26.7%) patients, respectively (HR = 0.85; 0.62-1.18). The comparative efficacy and safety of apixaban and dalteparin was not different in patients treated or not treated with anticancer agents. No effect on recurrent VTE, major bleeding or death was observed with inhibitors or inducers of P-glycoprotein and/or CYP3A4.

CONCLUSION

In our study, concomitant administration of anticancer agents had no effect on the risk of VTE recurrence or major bleeding in patients treated with apixaban or dalteparin for cancer-associated VTE.

Informations de copyright

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Déclaration de conflit d'intérêts

Conflict of interest statement M.V. reports personal fees from Pfizer, Bristol Myers Squibb and Bayer Healthcare, outside the submitted work; A.M. reports personal fees from Celgene, Sanofi, Pfizer-BMS, Leo Pharma, Daiichi Sankyo, Bayer Healthcare, Halozyme, AstraZeneca, Rovi, Merck Sharp & Dohme, Roche, Eli Lilly, Servier, Merck Serono, Incyte and Amgen, outside the submitted work; R.B. reports personal fees from Bristol Myers Squibb, Bayer, Daiichi Sankyo, Leo Pharma and Pfizer, outside the submitted work; M.V.H. reports receiving grant support from ZonMw Dutch Healthcare Fund, Boehringer Ingelheim, Pfizer-BMS, Bayer Healthcare and Leo Pharma, outside the submitted work; M.M. reports grants and personal fees from Novartis and personal fees from MSD, Pierre Fabre and BMS, outside the submitted work; G.V. reports personal fees from Bristol Myers Squibb, Pfizer, Bayer Healthcare and Daiichi Sankyo, outside the submitted work; C.B. reports personal fees from Bristol Myers Squibb, Bayer Healthcare, Daiichi Sankyo and Pfizer, outside the submitted work; G.A. reports personal fees from Bristol Myers Squibb, Pfizer, Bayer Healthcare and Daiichi Sankyo, outside the submitted work.