Background
Phase 3 open-label RCT (ADAM-VTE). 300 patients with active cancer and acute VTE (DVT or PE). US-based trial comparing oral apixaban to subcutaneous dalteparin for 6 months. Smaller than CARAVAGGIO but published simultaneously (JCO 2020). Powered for bleeding as primary endpoint (major + CRNMB), with VTE recurrence as secondary — a pragmatic design acknowledging cancer patients' high bleeding risk. Apixaban given without parenteral lead-in.
Interventions and follow up
Arm A: Apixaban 10 mg twice daily × 7 days, then 5 mg twice daily for 6 month
Arm B: Dalteparin 200 IU/kg once daily × 1 month, then 150 IU/kg once daily × 5 months (6 months total)
Primary endpoint: Major bleeding or CRNMB at 6 month
mFollow up: 6 month
Arm B: Dalteparin 200 IU/kg once daily × 1 month, then 150 IU/kg once daily × 5 months (6 months total)
Primary endpoint: Major bleeding or CRNMB at 6 month
mFollow up: 6 month
Results
Major bleeding or CRNMB: 20.2% (apixaban) vs 27.9% (dalteparin); OR 0.49, 95% CI 0.23–1.04 — P=.06 (borderline non-significant)
Major bleeding alone: 0% (apixaban) vs 1.4% (dalteparin) — no major bleeds with apixaban
Recurrent VTE: 3.4% (apixaban) vs 14.1% (dalteparin); OR 0.26, 95% CI 0.09–0.80 — P=.02
Major bleeding alone: 0% (apixaban) vs 1.4% (dalteparin) — no major bleeds with apixaban
Recurrent VTE: 3.4% (apixaban) vs 14.1% (dalteparin); OR 0.26, 95% CI 0.09–0.80 — P=.02
Adverse events
Main adverse events: No major bleeding events with apixaban (0% vs 1.4% dalteparin). CRNMB higher numerically but not statistically significant (P=.06 for composite). Recurrent VTE significantly lower with apixaban (3.4% vs 14.1%; P=.02). Fatal events: none in either arm attributable to study drug. GI bleeding numbers small. No hepatotoxicity signal.
Conclusions
In this US trial, apixaban was associated with no major bleeds, borderline reduction in combined bleeding, and significantly lower VTE recurrence compared to dalteparin in cancer patients, supporting apixaban as a safe and effective oral option for cancer-associated VTE.
Key Limitations
Key Limitations: Small sample size (n=300) — underpowered for the primary bleeding composite endpoint (P=.06). Open-label design. The primary endpoint was not met at P<.05 (though OR 0.49). Zero major bleeds in apixaban arm may be due to small sample rather than true risk absence. The markedly high VTE recurrence in dalteparin arm (14.1%) raises concerns about dalteparin dosing adherence in this US cohort. Concurrent CARAVAGGIO (n=1,170) is more definitive.
Clinical Context
ADAM-VTE was published simultaneously with CARAVAGGIO in JCO 2020, providing complementary US data. Together they established apixaban as the evidence-based preferred DOAC for cancer-VTE. ADAM-VTE is considered hypothesis-generating/supportive; CARAVAGGIO provides the primary evidence base. The absence of major bleeding with apixaban reinforces its favorable safety profile in cancer patients, including many with GI malignancies.
References