In both open-label trials, endpoint assessment was blinded according to the internationally accepted PROBE design (1). The inclusion of VTE incidental imaging findings made sense, as these events are prognostically important in cancer patients (2, 3).
Both studies reported a combined endpoint of efficacy and safety, in light of the increased risk of embolism and bleeding from cancer patients, and in this respect, both NOACs were equivalent to LMWH. The reduction of thromboembolism at the expense of higher rates of bleeding highlights the fact that every patient needs a benefit-risk assessment—even with LMWH treatment.
A LMWH treatment that lasts over several months impairs the quality of life of cancer patients. In the criticized studies, patient-initiated discontinuation of therapy was more common in the LMWH arm. This makes it clear that the recommendations for LMWH (which are also based on pharmaceutically-funded, open-label PROBE trials) as the standard of care are difficult to implement. When it comes to a benefit-to-harm ratio, patient preference for an oral therapeutic alternative must be recognized.
We neither work for pharmaceutical companies nor skew recommendations. We provide our expertise from years of clinical and scientific work with cancer patients, and an precise knowledge about the benefits and limitations of alternative therapies, not only to patients and medical colleagues but also to the research-based pharmaceutical industry. Expertise is indispensable for the correct execution and interpretation of clinical trials and for improved patient care.
We have clarified when a therapy with NOAC is problematic (4). Transparent disclosure of conflicts of interest does not preclude us from providing medical advice, but it does enable the reader to weigh recommendations against conflicts of interest, to make different recommendations, or to set up studies of their own without pharmaceutical promotion. In clinical research, vigilance, transparency, and critical dispute are important. Rejecting expert opinions and trial results solely on account of potential conflicts of interest is no longer appropriate in light of the increasing specialization in medicine as well as the complexity and costs of modern trial methodology.
On behalf of the authors
PD Dr. med. Jan Beyer-Westendorf
Department of Medicine I
Division of Hematology and Hemostaseology
University Hospital Carl Gustav Carus Dresden, Germany
Conflict of interest statement
PD Beyer-Westendorf has received speaking and/or consultant honoraria from EO Pharma, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Daiichi Sankyo, and Portola, travel expenses and registration fee reimbursement from LEO Pharma, Bayer, and Daiichi Sankyo, and fees (third-party account) for conducting commissioned clinical trials for LEO Pharma, Bayer, Pfizer, Boehringer Ingelheim, Janssen, Daiichi Sankyo, and Portola.
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|3.||van der Hulle T, den Exter PL, Planquette B, et al.: Risk of recurrent venous thromboembolism and major hemorrhage in cancer-associated incidental pulmonary embolism among treated and untreated patients: a pooled analysis of 926 patients. J Thromb Haemost 2016; 14: 105–13 CrossRef MEDLINE|
|4.||Beyer-Westendorf J, Klamroth R, Kreher S, Langer F, Matzdorff A, Riess H: Non-vitamin K antagonist oral anticoagulants (NOAC) as an alternative treatment option in tumor-related venous thromboembolism. Dtsch Arztebl Int 2019; 116: 31–8 VOLLTEXT|