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Everolimus added to consolidation therapy for AML
treatment. Although patients in whom drug delivery was inadequate (n=85) had a worse relapse-free survival (29%) there was no difference in relapse-free survival between patients with satisfactory drug delivery (n=63) at 41% and no everolimus treatment (n=99) at 40% (Online Supplementary Figure S4).
Discussion
In this trial there was no benefit of the addition of everolimus to post-induction chemotherapy, despite the pre-clinical in vitro and in vivo rationale for the use of this mTOR inhibitor. The main explanations appear to be the
Table 3. Recovery and supportive care in everolimus randomization. Randomization
Table 2. Clinical outcomes by treatment arm.
Everolimus
CR/CRi 99%
MRD positivity after 63%
course 2 (CR only)
30-day mortality 1%
60-day mortality 4%
5-year OS 45%
5-year RFS 29%
5-year cumulative 60% incidence of relapse
6-month death in CR 8%
5-year cumulative 11% incidence of death in CR
5-year survival after relapse 19%
5-year OS censored at SCT 57%
Control
99%
65%
1% 1% 58% 40% 54%
1% 6%
30%
66%
P-value 1.02 (0.09-11.2) 1.0
1.07 (0.50-2.33) 0.9
1.48 (0.19-11.7) 0.7 2.77 (0.70-11.0) 0.15 1.30 (0.94-1.81) 0.11 1.19 (0.90-1.59) 0.2 1.12 (0.82-1.52) 0.5
OR/HR & CI
Type of Care
Neutrophil recovery (median days from start of course)
Platelet recovery (median
days from start of course) Blood (mean n. of units)
Platelets (mean n. of units)
Antibiotics (mean days)
Hospitalization (mean days)
Hospitalization (median days)
† Logrank test. * Wilcoxon test.
P-value 0.4†
0.08†
0.006†
0.10†
Course
Everolimus Control
2 28 29 3 29 27
2 38 29
3 42 36
3.57 (1.36-9.42)
1.75 (0.83-3.70) 0.14
1.17 (0.81-1.70) 0.4
1.34 (0.87-2.06) 0.18
2 4.6 5.0 0.08* 3 6.3 6.1 0.5*
2 5.1 3.7 0.009*
3 6.4 5.5 0.4* 2 10.2 7.7 0.002*
0.009
3 12.5 10.8
2 25.2 22.3
3 24.8 23.5 2 25.5 23
3 25 24.5
0.14*
0.02*
0.3*
CR: complete remission; CRi: CR with incomplete blood count recovery; OS: overall survival; RE: relapse-free survival; SCT: stem cell transplantation.
AB
CD
Figure 4. Relapse, death in remission, relapse-free survival and overall survival within the everolimus randomisation: (A) Cumulative incidence of relapse; (B) cumu- lative incidence of death in remission; (C) relapse-free survival; (D) overall survival.
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