Apixaban, Dalteparin, in Active Cancer Associated Venous Thromboembolism, the ADAM VTE Trial

Abstract

Background: Currently, low molecular weight heparin is the guideline endorsed treatment of patients with cancer associated venous thromboembolism (VTE). While apixaban is approved for the treatment of acute VTE, there are limited data supporting its use in cancer patients. Methods: Patients with cancer associated acute VTE were randomly assigned to receive either apixaban 10 mg twice daily for 7 days followed by 5 mg twice daily or subcutaneous dalteparin (200 IU/kg for 1 month followed by 150 IU/kg once daily) for 6 months. The primary outcome was major bleeding. Secondary outcomes included VTE recurrence and a composite of major plus clinically relevant non-major bleeding. Results: Of the 300 patients who underwent randomization, 287 were included in the primary analysis. Of these, metastatic disease was present in 65.5% of subjects and 74% were receiving concurrent systemic cancer therapy. Colorectal, lung, pancreas, and breast cancers were the four most prevalent cancer types. Major bleeding occurred in 0 of the 142 patients (0%) in the apixaban group as compared with 3 of the 145 patients (2.1%) in the dalteparin group (p=0.9956). Recurrent VTE occurred in 5 patients (3.4%) in the apixaban group and 20 patients (14.1%) in the dalteparin group (difference in risk -10.7 percentage points) with a Hazard Ratio (HR) 0.26, (95% CI, 0.09 - 0.80, p = 0.0182). Major plus clinically relevant non-major bleeding were similar at 9% for both groups. There were no mortality differences comparing apixaban (15.9%) and dalteparin (10.6%) groups at 6 months (HR 1.36, 95% CI 0.79 - 2.35). Monthly quality of life surveys favored apixaban therapy for many measures including: concern for excess bruising, stress, irritation, burden of delivery, and overall satisfaction with anticoagulant therapy (p<0.05). Monthly bruising questionnaire favored apixaban at each interval (p<0.002). Conclusions: Oral apixaban therapy was associated with very low rates of bleeding and significantly lower VTE recurrence with superior quality of life outcome measures compared to parenteral dalteparin in the treatment of cancer associated VTE. These data support the clinical utility of apixaban for the acute treatment of VTE in this patient population. Table. Table. Disclosures No relevant conflicts of interest to declare.

Comparison of apixaban to rivaroxaban and enoxaparin in acute cancer‐associated venous thromboembolism

“…In the current study, major bleeding rates were similar in patients treated with apixaban, rivaroxaban, and enoxaparin. These results are consistent with RCT findings which also showed similar rates of major bleeding of apixaban and rivaroxaban compared to dalteparin . There was no major bleeding event in the apixaban arm of ADAM‐VTE trial, while, in our study, 5.8% of apixaban treated patients had major bleeding at 6 months.…”

“…These results are consistent with RCT findings which also showed similar rates of major bleeding of apixaban and rivaroxaban compared to dalteparin . There was no major bleeding event in the apixaban arm of ADAM‐VTE trial, while, in our study, 5.8% of apixaban treated patients had major bleeding at 6 months. The major bleeding rate at 6 months in the rivaroxaban arm of the current study (6.6%) corresponds with SELECT‐D trial results (6.0%).…”

“…Note VTE recurrence with apixaban, rivaroxaban, and enoxaparin was similar when examined in the long‐term analysis and at three and 6 months. In recent RCTs of Ca‐VTE, apixaban and rivaroxaban showed better efficacy compared to the LMWH dalteparin . In the ADAM‐VTE trial, the rate of VTE recurrence with apixaban was lower than in this study (0.7% vs 6.5%), and the rate of VTE recurrence with dalteparin was comparable to our 6 month outcome with enoxaparin (6.3% vs 4.3%).…”

“…In recent RCTs of Ca‐VTE, apixaban and rivaroxaban showed better efficacy compared to the LMWH dalteparin . In the ADAM‐VTE trial, the rate of VTE recurrence with apixaban was lower than in this study (0.7% vs 6.5%), and the rate of VTE recurrence with dalteparin was comparable to our 6 month outcome with enoxaparin (6.3% vs 4.3%). In the SELECT‐D trial, VTE recurrence rate for rivaroxaban (4%) was almost identical with the 6 month recurrence rate of the current study (3.7%).…”

“…Low molecular weight heparin (LMWH) has been equally or more effective than, and as safe as, vitamin K antagonists in patients with Ca‐VTE, and therefore was recommended as the first line of anticoagulation for this group of patients . However, recent randomized clinical trials (RCTs) of direct oral anticoagulant(s) (DOACs) in Ca‐VTE patients changed these recommendations . Until now, no direct comparison between DOACs in Ca‐VTE patients has been reported.…”