Efficacy

Overall survival (OS)

Adding DAURISMO significantly extended OS2
DAURISMO (glasdegib) + LDAC nearly doubled median OS vs LDAC alone with a median follow-up of approximately 20 months2
*HR based on the Cox proportional hazards model stratified by cytogenetic risk.
1-sided P value from log-rank test stratified by cytogenetic risk.
CI=confidence interval; HR=hazard ratio.
The probability of survival at 1 year was nearly 40% with DAURISMO + LDAC3
OS at 1 year was a prespecified, exploratory endpoint, but there was no prespecified statistical procedure controlling for type 1 error (false positive) rate.
 
References
  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.3.2020. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed January 13, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  2. Daurismo [Prescribing Information]. New York, NY: Pfizer Inc.; 2020.
  3. Data on file. Pfizer Inc., New York, NY.

OS subgroup analyses

OS exploratory subgroup analysis across a range of patients2
These subgroup analyses were not prespecified and not powered to detect statistical significance. There is a slight imbalance toward good/intermediate-risk cytogenetics in the DAURISMO + LDAC arm versus the LDAC arm.
The HRs associated with each of these analyses are unreliable due to the very small sample sizes of each subgroup, and the CIs may not be interpretable. HRs and CIs are provided for transparency. These data could represent chance findings and should be interpreted with caution.
The sample sizes for the subgroups of baseline age <65 years old, race other than white, and the prognostic risk factor as favorable were too small (n≤10) for analysis.
The HR values presented were based on the unstratified analysis for all subgroups except for the AML population. Prognostic risk factor (good/intermediate vs poor) from interactive voice response system was used as a stratification factor in the stratified analysis for the AML population.
OS exploratory subgroup analysis in patients with sAML2
Analyses of OS in the subgroup of patients with sAML and in age-defined subgroups were post hoc and not powered to detect statistical significance. Small patient numbers and lack of multiplicity adjustments can be a limitation of these analyses.
The HRs associated with these analyses are unreliable due to the very small sample size. HRs and CIs are provided for transparency. The estimated median OS results in these exploratory subgroups may be biased due to censoring at the time of the analysis.
  • 51% of patients in the DAURISMO + LDAC arm had sAML3
  • Patients with sAML were allowed 1 prior regimen (eg, azacitidine or decitabine) for the treatment of prior hematologic disease2
  • Approximately 28% of patients with sAML in the DAURISMO + LDAC arm were treated with a prior HMA for MDS2
OS exploratory subgroup analyses in patients ≥75 and <75 years2†
*HR based on the Cox proportional hazards model.2
All patients in the BRIGHT AML 1003 trial were aged ≥55 years. Patients were eligible for the BRIGHT AML 1003 trial if they met at least 1 of the following criteria, which precluded the use of intensive chemotherapy: (a) aged ≥75 years; (b) severe cardiac disease (LVEF <45%); (c) ECOG PS=2; or (d) creatinine >1.3 mg/dL.2,3
ELN=European LeukemiaNet.
 
References
  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.3.2020. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed January 13, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  2. Data on file. Pfizer Inc., New York, NY.
  3. Daurismo [Prescribing Information]. New York, NY: Pfizer Inc.; 2020.

Response assessments

With DAURISMO, more patients achieved a CR2
These analyses were not powered to detect statistical significance. Small patient numbers and lack of multiplicity adjustments can be a limitation of these analyses.
CR is the endpoint based on a patient’s hematologic response that is most associated with clinical benefit in AML.
*These data do not include stable disease.
MR=minor response. Protocol definition: 1) Neutrophils: N/A 2) Platelets: N/A, and 3) Bone marrow blasts: >25% decrease from start.
CR=complete response; CRi=Morphologic CR with incomplete blood count recovery; MLFS=Morphologic leukemia-free state; PR=partial remission; PRi=Partial remission with incomplete blood count recovery.
  • 15.6% of patients in the DAURISMO + LDAC arm (n=12/77; 95% CI, 8.3-25.6) had SD vs 23.7% in the LDAC-alone arm (n=9/38; 95% CI, 11.4-40.2) as their best response2
  • CR was the most common response with DAURISMO + LDAC (18.2% vs 2.6% with LDAC alone)2
 
Median OS in patients who did and did not achieve a CR2
Analyses of OS in CR-defined subgroups were not prespecified and not powered to detect statistical significance. Small patient numbers and lack of multiplicity adjustments can be a limitation of these analyses. Response status is not a baseline characteristic and, therefore, not subject to randomization or stratification. These data are subject to length-biased sampling, which may lead to an overestimation of median survival.
  • In the 14 patients who achieved a CR, median OS with DAURISMO + LDAC was 26.8 months (95% CI, 12.3-not reached)2
  • In the 63 patients who did not achieve a CR, median OS with DAURISMO + LDAC was 5.0 months (95% CI, 3.5-9.0)2
 
References
  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.3.2020. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed January 13, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  2. Data on file. Pfizer Inc., New York, NY.

Time to response

Most responses with DAURISMO + LDAC occurred within the first 6 months on treatment2
 
Analyses were not prespecified and not powered to detect statistical significance. Small patient numbers and lack of multiplicity adjustments can be limitations of these analyses.
*Best individual response included CR, CRi, MLFS, PR, PRi, and MR. SD was excluded.
Of the patients who achieved their best individual response at cycle 4 or later, 30% (3/10) achieved CR, 40% (4/10) achieved CRi, 10% (1/10) achieved MLFS, 10% (1/10) achieved PR, and 10% (1/10) achieved PRi.
  • In the DAURISMO + LDAC arm, the median time to best individual response* was 1.9 months (range, 0.6-7.6 months; n=32)2†
  • The median duration of treatment in the DAURISMO + LDAC arm was 2.73 months (range, 0.10-31.93 months; n=84) vs 1.54 months (range, 0.20-7.85 months; n=41) in the LDAC-alone arm3
  • Thirty-two patients (38%) were treated with DAURISMO + LDAC for at least 6 months and 14 patients (17%) were treated for at least 1 year (n=84)3
Best individual response included CR, CRi, MLFS, PR, PRi, and MR. SD was excluded.
 
References
  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.3.2020. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed January 13, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  2. Data on file. Pfizer Inc., New York, NY.
  3. Daurismo [Prescribing Information]. New York, NY: Pfizer Inc.; 2020.

Transfusion independence

Post hoc analyses of transfusion independence2,3
Analyses were post hoc and not powered to detect statistical significance. Small patient numbers and lack of multiplicity adjustments can be limitations of these analyses.
*Transfusion independence was defined as patients who had ≥8 weeks (56 consecutive days) without any type of transfusion at any point in the study. All other patients were considered transfusion dependent. Transfusion independence was not assessed at baseline.
This post hoc analysis included all patients who received ≥1 study drug dose (N=110).
Post hoc analyses of exposure-adjusted transfusion rates2,3‡§
Exposure-adjusted transfusion rates were calculated as the sum of the number of on-study transfusions/total number of patient-days. Number of on-study transfusions includes transfusions from cycle 1, day 1 to the end of treatment. Total number of patient-days was the sum of the total time on treatment for all patients in each treatment arm.
§This post hoc analysis included all patients who received ≥1 study drug dose (N=110).
PRBC=packed red blood cell.
 
References
  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.3.2020. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed January 13, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  2. Data on file. Pfizer Inc., New York, NY.
  3. Wang ES, Heuser M, Montesinos P, et al. Glasdegib with LDAC in newly diagnosed patients with acute myeloid leukemia (AML) unsuitable for intensive chemotherapy: effects on transfusions and marrow recovery vs LDAC alone. Poster PF272 presented at: European Hematology Association 24th Congress; June 13-16, 2019; Amsterdam, the Netherlands.