Study Design
Verbalize study design. Was cross-over allowed?
See Figure S1. Study design and NO cross-over
What is the average age, age range and % over 65 years old?
average age = 68 years
age range = (55-86)
%>65 years = 72%
What was the most common serious adverse events?
Infections in 17% of patients in the CC-486 group and 8% of patients in the placebo group
What was the median time from CR/CRI to randomization?
85 days
Andrew Wei is the first author on the Quazar manuscript. What country, city, hospital and university does he work at?
Australia, Melbourne, Alfred Hospital, Monash University
What ANC and platelet count was needed for Quazar inclusion criteria?
ANC ≥0.5 × 109/L
Platelet count ≥20 × 109/L
What percent of patients had myelodysplastic related changes?
19%
Which TEAE (Treatment-emergent adverse event) was most frequent in leading to dose-reduction in Onureg?
Neutropenia 6%
[Table S7]
What was the most common reason for the 83 that were screened but did not undergo randomization?
Most patients (47 of 83) who were ineligible after screening had exceeded the acceptable 4-month period from attainment of remission to randomization.
What percent of patients had restoration of CR with escalated dose of Onureg?
10 of 43 patients (23%) in the CC-486 group had restoration of CR status while receiving the escalated dosing regimen.
Could patients who received HMAs for MDS be enrolled into the Quazar trial?
Patients were excluded if they received therapy with HMA for MDS and went on to develop AML within four months of discontinuing the therapy with HMA
What % of patients had ECOG 2 or 3?
8% [table 1 & S1]
In CSR: ECOG 3 --> CC-486 =0 and placebo =2
What TEAE (treatment-emergent adverse event) was most commonly reported with Onureg during escalated (21-day) dosing?
Febrile neutropenia 24%
[table S9]
What were the most common agents used for consolidation?
cytarabine (in 377 of 378 patients)
idarubicin (in 95 of 378)
daunorubicin (in 37 of 378).
What percent of patients in each arm received at least one course of subsequent treatment after discontinuation of trial therapy?
CC-486: 137 patients (58%)
Placebo: 170 patients (73%)
(page 2534)
What was the frequency of biopsy assessments in the Quazar trial?
Every 3 cycles during the first 24 cycles, at cycles 30 and 36, then as clinically indicated.
What number of patients received 3 cycles of consolidation?
19 (6 in CC-486 and 13 in placebo)
Describe the deaths reported in the Quazar article.
CC-486 group, 9 patients (4%):
- 2 each -->sepsis and cerebral hemorrhage
- 1 each -->sepsis w/ multiorgan failure, intracranial hemorrhage, cardiogenic shock, aspiration pneumonia, and suicide.
Placebo group, 4 patients (2%): two died from multiorgan failure, one from cerebral hemorrhage, and one from general health deterioration.
How many patients completed the QOL assessments at the time of median OS for Onureg?
At 24 months, 70 patients for Onureg and 34 patients in the placebo arm completed QOL assessments.
[figure S3]
What percent of patients in each arm of the Quazar trial received transplant as their subsequent therapy?
Onureg 6% (n=15)
Placebo 14% (n=32) [table S10]
How was Relapse blast percentage defined in Quazar as compared to AML guidelines?
Patients who were identified as having AML relapse with 5 to 15% blasts in blood or bone marrow during receipt of CC-486 or placebo [page 2528] vs 20%
What percent of total patient population were “ineligible for HSCT” because of “patient decision”?
11%
[table S1, page 12]
For Onureg patients that received >13 cycles, did the percent of reported hematologic adverse events decrease, stay same or increase?
Stayed the same between cycles 1-12 (34-37%) then increased percentage reported after cycle 13 (56%) [table S4]
Why were hazard ratios are not provided for OS in the Quazar manuscript?
The proportional hazards assumption appeared to be violated, as indicated by the significant treatment-by-time interaction. [page 2529 statistical analysis]
At time of publication, which two therapy options are approved in the EU for maintenance?
Histamine dihydrochloride–interleukin-2 combination therapy and Midostaurin