Rivaroxaban Sotorasib Interaction Study

Venous thromboembolic Events (VTEs) are common in lung cancer patients with an incidence of \>15%, requiring anticoagulant treatment or prophylaxis. Although direct acting oral anticoagulants (DOACs) are the agents of first choice due to ease and patient friendliness, these drugs are often avoided in cancer patients due to suspected pharmacokinetic drug-drug interactions with oncolytic drugs. Sotorasib is the first KRASG12C inhibitor that has been approved by the US \[FDA\] and EU \[EMA\] for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC. Sotorasib has a potential to cause CYP3A-mediated drug-drug interactions due to induction of CYP3A and inhibition of P-GP. Rivaroxaban is the most frequently prescribed DOAC in the Netherlands. As rivaroxaban is a substrate for this enzyme and efflux pump, sotorasib may increase or decrease the exposure to rivaroxaban and, thus, impact its benefit-to-risk ratio. To enable safe combination of sotorasib and rivaroxaban, it is pivotal to investigate the magnitude of the pharmacokinetic interaction between these drugs.