Practical recommendations to combine small-molecule inhibitors and direct oral anticoagulants in patients with nonsmall cell lung cancer

Otten, L.S.; Piet, Berber; Heuvel, Michel M. van den; Marzolini, Catia; Geel, Robin M.J.M. van; Gulikers, Judith L; Burger, David M.; Leentjens, Jenneke; Heine, Rob ter

doi:10.1183/16000617.0004-2022

Cited by 8 publications

(7 citation statements)

References 44 publications

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“…Importantly, there is no evidence at this time that adjusting the DOAC dose in response to measured levels will actually lead to better clinical outcomes 16,17 . Others have promoted adjusting the dose based on measurements and/or expected drug interactions 43 . In general, we advise caution and do not promote this practice systematically.…”

Section: Five Considerationsmentioning

confidence: 97%

“…16,17 Others have promoted adjusting the dose based on measurements and/or expected drug interactions. 43 In general, we advise caution and do not promote this practice systematically. While the observed ranges from landmark trials can be used to interpret an individual patient's exposure, there are no data in support of altering the dose in response to these ranges to improve clinical outcome.…”

Section: Five Considerationsmentioning

confidence: 98%

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Pharmacokinetic drug–drug interactions with direct anticoagulants in the management of cancer‐associated thrombosis

Linden

Vanassche

Cutsem

et al. 2023

Brit J Clinical Pharma

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Drug-drug interactions (DDIs) are common in cancer management and complicate the choice of anticoagulation in cancer-associated thrombosis. Cancer confers an increased risk of thrombotic events. Also, more bleeding events are observed in those who receive anticoagulation compared to those without cancer. In the treatment of cancer-associated thrombosis, direct oral anticoagulants (DOACs) have been found to be at least as effective as low-molecular weight heparins, which became the standard of care after several trials demonstrated superiority over vitamin K antagonists.Non-inferiority compared to low-molecular weight heparins has been shown for rivaroxaban, edoxaban and apixaban with a signal of fewer recurrent thrombotic events, albeit with an increase in bleeding events. Yet, potentially major pharmacokinetic drug-drug interactions have been identified as a reason to withhold DOACs and to rather choose an alternative. Practical guidance on what constitutes a major pharmacokinetic interaction and/or how to deal with these interactions in clinical practice is limited. Hence, here we have provided a framework to allow clinicians to better deal with pharmacokinetic drug-drug interactions between DOACs and cancer therapies in the management of cancer-associated thrombosis. In this review we have discussed the current literature, how the pharmacokinetic profile links to the label information on DDI, and have provided a practical proposal, applied to a clinical case. K E Y W O R D S anticoagulation, cancer, cancer-associated thrombosis, direct oral anticoagulants, drug-drug interactions 1 | INTRODUCTION Cancer patients are at increased risk for thromboembolism. 1 Various factors explain the increased susceptibility to clots, including the type, location and staging of the cancer itself. Other determinants such as surgical interventions, indwelling catheters and cancer therapies also play a major role. Cancer-associated thrombosis (CAT) is a prevalent finding in cancer patients. 2 It is the second most common cause of death in cancer patients, following cancer-related death by a large margin. 3 Importantly, the risk of an incidental venous thrombo-embolic event (VTE) is higher in cancer patients than in those without. Moreover, higher risks of both recurrent VTE and bleeding events are observed in cancer patients who receive anticoagulation compared to the general population. 4 Historically, CAT was treated with the vitamin K antagonist (VKA) warfarin. This treatment paradigm altered a first time after trials comparing VKA with low-molecular weight heparins (LMWH), among which the CLOT trial was the first. 5 A clear benefit was observed in favour of LMWH versus VKA. LMWH-treated patients incurred a similar major bleeding risk, yet LMWH provided superior thrombotic protection compared to VKA. As a result, LMWH have been the standard of care in the

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Section: Five Considerationsmentioning

confidence: 97%

Section: Five Considerationsmentioning

confidence: 98%

Pharmacokinetic drug–drug interactions with direct anticoagulants in the management of cancer‐associated thrombosis

Linden

Vanassche

Cutsem

et al. 2023

Brit J Clinical Pharma

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“…Most of the time, drug-drug interactions occur between tyrosine kinase inhibitors [48,87,118]. Other groups are small-molecule inhibitors [119], monoclonal antibodies i.e., alemtuzumab, hormonal agents, i.e., enzalutamide, and immune-modulating agents, i.e., cyclosporine [118]. It is important to highlight that DOACs will interfere differently with antineoplastic agents, with apixaban having the lowest potential to interact with antineoplastic agents [120].…”

Section: Could Doacs Be Used As a Substitute For Classic Anticoagulan...mentioning

confidence: 99%

Direct-Acting Oral Anticoagulant Therapy in Cancer Patients—A Review

Górnicki

Bułdyś

Zielińska³

et al. 2023

Cancers

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Venous thromboembolism (VTE) is an important aspect in cancer patients. There are various pharmacological methods used for thrombotic event treatment. DOACs (direct-acting oral anticoagulants) are gaining popularity among both physicians and researchers and are slowly starting to replace VKAs (vitamin K antagonists), thus becoming a substitute or alternative option for LMWHs (low-molecular-weight heparins). In this article, we present DOACs’ main therapeutic advantages and disadvantages in patients with cancer. The only major concern with using DOACs is the higher risk of bleeding; however, there are discrepancies in this matter. There are still some types of cancer for which DOACs are not recommended. Specific cancer types may influence the efficacy of DOAC therapy. Additionally, race and ethnicity may affect therapy in cancer patients with DOACs. A sizeable number of clinical trials are focused on comparing DOACs with other anticoagulants. The current guidelines of different scientific associations are not unanimous in their DOAC assessments. There is still a need for more evidence of DOACs’ potential advantages over other methods of anticoagulation in cancer patients to facilitate their position in this recommendation. This literature review presents the current state of knowledge about the use of DOACs in patients with neoplastic growth.

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“…As examples, they propose taking into account the risk for anemia with alectinib, as well as the risk for metabolic diseases with lorlatinib (to be balanced with respect to the frequently young age at NSCLC diagnosis). Furthermore, they recommend considering the pharmacological interactions in patients receiving polypharmacotherapy for comorbidities (e.g., drugs with central nervous system activity in patients with psychiatric disorders or direct-acting oral anticoagulants (DOACs) [22]).…”

Section: Patients' Selection Criteriamentioning

confidence: 99%

Sharing Experience with Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitors in Lung Cancer: An Italian Expert Panel Discussion

Gridelli,

Tiseo,

Cortinovis

et al. 2023

Current Oncology

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Background: ALK tyrosine kinase inhibitors (TKIs) have revolutionized the treatment and largely improved the survival outcomes of patients with NSCLC harboring ALK rearrangements. Different ALK TKI compounds have demonstrated antitumor activity in these patients and are available in clinical practice. However, clinical expertise across countries varies according to local regulatory approval of different drugs, identifying multiple treatment scenarios to comply with international guidelines and clinical practice. Methods: A virtual webinar was held on July 2023 to discuss the state of the art and future perspectives in the treatment of ALK rearrangement in advanced NSCLC in Italy. The faculty hosting the webinar was composed of eight medical oncologists from different regions of Italy with clinical expertise in treating patients with lung cancer. Live-shared notes were used to produce a report to serve as the basis of a review manuscript on the topic. Results: Alectinib and brigatinib are the preferred front-line treatment options in Italy, pending approval of the front-line medicine lorlatinib, which would be considered among the choices. Due to a local regulatory limitation of second-line lorlatinib, which is not allowed after front-line brigatinib, alectinib is commonly the preferred front-line choice to follow a sequence of alectinib, followed by lorlatinib, followed by platinum plus pemetrexed chemotherapy. Age and performance status were not considered per se as clinical features influencing treatment choice. However, treatment compliance is deemed a relevant factor in decision making with regard to the number of pills to be administered. In general, given the availability of alternative choices, the spectrum of patients’ comorbidities and polypharmacotherapy interactions should be taken into account in treatment selection according to the toxicity profile of each compound. In addition, several issues were debated with regard to improving treatment outcomes, including testing, brain metastases, and management of an oligoprogressive disease. Conclusions: The treatment scenario of ALK-positive disease is dynamically evolving. Furthermore, not all FDA- and EMA-approved compounds are approved in Italy with the same indications. This influences therapeutic opportunities and increases the need for greater clinical expertise to help and guide treatment selection.

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Practical recommendations to combine small-molecule inhibitors and direct oral anticoagulants in patients with nonsmall cell lung cancer

Cited by 8 publications

References 44 publications

Pharmacokinetic drug–drug interactions with direct anticoagulants in the management of cancer‐associated thrombosis

Pharmacokinetic drug–drug interactions with direct anticoagulants in the management of cancer‐associated thrombosis

Direct-Acting Oral Anticoagulant Therapy in Cancer Patients—A Review

Sharing Experience with Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitors in Lung Cancer: An Italian Expert Panel Discussion

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