E2906 phase III: Clofarabine vs intensive 7+3 chemotherapy in fit older adults with ND AML

Results from the open-label, randomized, phase III E2906 trial (NCT02085408), evaluating clofarabine monotherapy (n = 364) vs standard intensive daunorubicin + cytarabine (7+3; n = 363) in fit older adults with newly diagnosed (ND) acute myeloid leukemia (AML), were published in Blood Neoplasia by Foran et al. The primary endpoint was overall survival (OS) by weighted analyses.

Key data: At a median follow-up of 58.6 months, OS was inferior with clofarabine vs 7+3 (median, 10.4 vs 12.4 months; hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.10–1.47; p = 0.04), though not significant on multivariate analysis (HR, 1.11; 95% CI, 0.92–1.35; p = 0.28). Among measurable residual disease (MRD)-positive patients, OS was worse with clofarabine vs cytarabine consolidation (HR, 1.99; 95% CI, 1.07–3.71; p = 0.03). Clofarabine had lower Grade 4–5 nonhematologic toxicity during induction (18% vs 27%; p = 0.01) and consolidation (7% vs 21%; p < 0.001), but more transient Grade 3/4 serum transaminase elevations (32.2% vs 13.2%; p < 0.001).

Key learning: Clofarabine did not lower 30-day induction mortality or improve survival vs 7+3 in fit older adults with ND AML, reinforcing the importance of randomized evaluation of lower-intensity regimens. Optimized consolidation remains important for MRD-positive patients.