The purpose of this study is to learn whether apixaban is well-tolerated and acceptable as anticoagulant therapy, when administered to patients with advanced or metastatic cancer and at increased risk for venous thromboembolic events. Demonstration of a favorable benefit:risk profile could lead to significant reduction in this serious and sometimes fatal complication of ongoing cancer and its treatment.
BACKGROUND: Cancer patients receiving chemotherapy, biologic, and molecular targeted therapies are at increased risk of venous thromboembolism (VTE). Currently available anticoagulants (ACs) are not well suited to prevent VTE in such patients. Vitamin K antagonist oral ACs require frequent lab monitoring and low molecular weight heparins require daily subcutaneous injection. There is concern for bleeding with ACs. Apixaban (A) is a new antithrombotic agent which inhibits activated coagulation Factor X, is taken orally, and does not require lab monitoring. Trials to prevent post-operative VTE in orthopedic surgery showed that A was effective and safe. We wanted to assess the feasibility of A in cancer. METHODS: In a randomized phase II trial, patients with metastatic cancer on 1st or 2nd line chemotherapy received study drug once daily for 12 weeks; either 5, 10 or 20 mg of A, or placebo. The primary outcome measure was the proportion of patients remaining free of major bleeding (MB), clinically relevant non-major bleeding (CRNMB), VTE, and grade ≥3 adverse events considered to be probably/definitely related to study drug (AE*). After 125 patients were recruited, the sponsor eliminated further randomization to the 10 and 20 mg arms, to add experience with the 5 mg dose currently under evaluation for VTE prevention in other conditions. Data on the first 125 patients are reported. RESULTS: The study population was 50% male; 88% had ECOG performance status 0 or 1. The most common cancers were breast, colon, pancreas, and myeloma. 23% had liver metastases. Approximately 80% of A patients completed 12 weeks of treatment. The numbers of patients with events were: CONCLUSIONS: Apixiban was well tolerated in patients with advanced cancer on chemotherapy. Major bleeding, thrombosis, and drug-related SAEs were very low. These results support further study of A in phase III trials for VTE prevention in cancer patients.
CONTEXTE: Les patients cancéreux recevant une chimiothérapie courent un risque accru de thrombose. Apixaban, un inhibiteur du facteur Xa, est la voie orale et ne nécessite pas la surveillance de laboratoire.
OBJECTIFS: Une étude pilote a été réalisée afin d'évaluer si l'apixaban serait bien tolérée et acceptable chez les patients cancéreux recevant une chimiothérapie.
PATIENTS / METHODES: Les sujets recevant une chimiothérapie de première ou de deuxième ligne pour le poumon avancé ou métastatique, du sein, gastro-intestinal, de la vessie, des ovaires ou de la prostate, le cancer d'origine inconnue, le myélome ou lymphomes sélectionnés ont été randomisés à 5 mg, 10 mg ou 20 mg une fois par jour de l'apixaban, soit un placebo, en double aveugle pendant 12 semaines. L'utilisation du médicament à l'étude a commencé dans les 4 semaines suivant le début de la chimiothérapie. Le critère principal était soit saignement majeur ou non-major saignements cliniquement importants (CRNM). Les critères secondaires incluaient la thromboembolie veineuse (TEV) et de grade III ou événements indésirables plus élevés liés au médicament à l'étude. Trente-deux patients ont reçu 5 mg, 30 patients 10 mg, 33 patients de 20 mg et 30 patients sous placebo. Dans ces groupes, il y avait 0, 0, 2 et 1 saignements majeurs, respectivement. Les données correspondantes pour CRNM saignements étaient de 1, 1, 2 et 0. Le taux de saignements majeurs dans les 93 patients apixaban était de 2,2% (95% intervalle de confiance de 0,26 à 7,5%). Il n'y avait aucun saignements mortels. Trois patients du groupe placebo ont eu TEV symptomatique.
CONCLUSIONS: L'apixaban a été bien toléré dans notre population d'étude. Ces résultats confirment d'autres études de l'apixaban dans les essais de phase III pour prévenir la TEV chez les patients cancéreux recevant une chimiothérapie.
The purpose of this study is to learn whether apixaban is well-tolerated and acceptable as anticoagulant therapy, when administered to patients with advanced or metastatic cancer and at increased risk for venous thromboembolic events. Demonstration of a favorable benefit:risk profile could lead to significant reduction in this serious and sometimes fatal complication of ongoing cancer and its treatment.
