Lo-Coco 2013
Trial question
What is the role of all-trans retinoic acid plus arsenic trioxide among patients with acute promyelocytic leukemia?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
51.0% female
49.0% male
N = 156
156 patients (80 female, 76 male).
Inclusion criteria: patients with acute promyelocytic leukemia classified as low-to-intermediate risk.
Key exclusion criteria: age < 18 and ≥ 71 years, uncontrolled life-threatening infections, severe non-controlled pulmonary or cardiac disease, other active malignancy at the time of study entry, pregnancy.
Interventions
N=77 ATRA-arsenic trioxide (all-trans retinoic acid plus arsenic trioxide for induction and consolidation therapy).
N=79 ATRA-chemotherapy (standard all-trans retinoic acid-idarubicin induction therapy followed by three cycles of consolidation therapy with all-trans retinoic acid plus chemotherapy and maintenance therapy with low-dose chemotherapy and all-trans retinoic acid).
Primary outcome
Event-free survival at 2 years
97%
86%
97.0 %
72.8 %
48.5 %
24.3 %
0.0 %
ATRA-arsenic
trioxide
ATRA-chemotherapy
Significant
increase ▲
NNT = 9
Significant increase in event-free survival at 2 years (97% vs. 86%; AD 11%, 95% CI 2 to 22).
Secondary outcomes
Significant increase in overall survival at 2 years (99% vs. 91%; AD 8%, 95% CI 1.25 to 14.75).
No significant difference in disease-free survival at 2 years (97% vs. 90%; AD 7%, 95% CI -1.59 to 15.59).
No significant difference in relapse at 2 years (1% vs. 6%; ARD -5, 95% CI -13.3 to 3.3).
Safety outcomes
No significant difference in kinetics of minimal residual disease.
Significant difference in hematologic toxicity (26 episodes vs. 59 episodes) and grade 3 or 4 hepatic toxicity (63% vs. 6%).
Conclusion
In patients with acute promyelocytic leukemia classified as low-to-intermediate risk, ATRA-arsenic trioxide was superior to ATRA-chemotherapy with respect to a event-free survival at 2 years.
Reference
Lo-Coco F, Avvisati G, Vignetti M et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013 Jul 11;369(2):111-21.
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