{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:54:49Z","timestamp":1790394889078,"version":"4.1.0"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T00:00:00Z","timestamp":1718064000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T00:00:00Z","timestamp":1718064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Funded by Academic Alliance Fund"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Br J Cancer"],"published-print":{"date-parts":[[2024,8,24]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Small-molecule inhibitors (SMIs) have revolutionised the treatment of non-small cell lung cancer (NSCLC). However, SMI-induced drug\u2013drug interactions (DDIs) with frequently co-administered direct oral anticoagulants (DOACs), increase thromboembolic and bleeding risks. This study investigated and proactively managed the consequences of DOAC-SMI DDIs.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This prospective, observational study enrolled patients with NSCLC concomitantly using a DOAC and SMI. The primary outcome was the proportion of patients with DOAC plasma trough (C<jats:sub>trough<\/jats:sub>) and peak (C<jats:sub>peak<\/jats:sub>) concentrations outside expected ranges. Secondary outcomes included DOAC treatment modifications, incidence of bleeding and thromboembolic events and feasibility evaluation of pharmacokinetically guided DOAC dosing.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Thirty-three patients were analysed. Thirty-nine percent (13\/33) had DOAC C<jats:sub>trough<\/jats:sub> and\/or C<jats:sub>peak<\/jats:sub> were outside the expected ranges in 39% (13\/33). In 71% (5\/7) of patients with DOAC concentrations quantified before and during concurrent SMI use, DOAC C<jats:sub>trough<\/jats:sub> and\/or C<jats:sub>peak<\/jats:sub> increased or decreased &gt;50% upon SMI initiation. In all patients in whom treatment modifications were deemed necessary, DOAC concentrations were adjusted to within the expected ranges.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Proactive monitoring showed that a substantial proportion of patients had DOAC concentrations outside the expected ranges. DOAC concentrations were successfully normalised after treatment modifications. These results highlight the importance of proactive monitoring of DOAC-SMI DDIs to improve treatment in patients with NSCLC.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1038\/s41416-024-02744-1","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T16:03:56Z","timestamp":1718121836000},"page":"481-490","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Proactive monitoring of drug\u2013drug interactions between direct oral anticoagulants and small-molecule inhibitors in patients with non-small cell lung cancer"],"prefix":"10.1038","volume":"131","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8844-6992","authenticated-orcid":false,"given":"Judith L.","family":"Gulikers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1225-4740","authenticated-orcid":false,"given":"Leila-Sophie","family":"Otten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3521-2535","authenticated-orcid":false,"given":"Lizza E. 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Gilead under negotiation. All payments were paid to the institution. All unrelated to this work. Advisory boards: Amgen, Boehringer Ingelheim, Lilly, Novartis, Pfizer, Takeda, Merck, Janssen, MSD, Anheart. All payments were paid to the institution. Member guideline committees: Dutch guidelines on NSCLC, brain metastases and leptomeningeal metastases (self), ESMO guidelines on metastatic NSCLC and systemic therapy, vice-chair scientific committee Dutch Thoracic Group SCLC (non-financial). Other (non-financial): secretary NVALT studies foundation, subchair EORTC metastatic NSCLC systemic therapy, vice-chair of scientific committee Dutch Thoracic Group. Local PI of clinical trials: AstraZeneca, GSK, Novartis, Merck, Roche, Takeda, Blueprint, Mirati, Abbvie, Gilead, MSD, Merck. All payments to the institution. Speaker educationals\/webinars: AstraZeneca, Bayer, Lilly, MSD, high5oncology, Takeda, Janssen, GSK, Sanofi, Pfizer (Inst), Medtalks, Benecke, VJOncology, Medimix (self). All payments were paid to the institution with the exception of Medtalks, Benecke, VJOncology, Medimix. Dr. J Leentjens reports grants or contracts from BMS-Pfizer, Viatris, and AstraZeneca, all unrelated to this work and paid to her institution. Dr. R ter Heine has received research funding from AMGEN for a clinical study investigating the interaction between sotorasib and rivaroxaban. All other authors declare that they have no known competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Ethics approval was given by the medical ethical committee of Maastricht UMC+ (NL78003.068.21). All participating patients signed informed consent before entering the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All participating patients signed informed consent before entering the study and their data were pseudo-anonymized.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}