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.
 
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.
  3. Data on file. Pfizer Inc., New York, NY.

1-year OS

The 1-year overall survival (OS) rate was 4-fold higher with DAURISMO + LDAC vs LDAC alone2
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. Data on file. Pfizer Inc., New York, NY.

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 sAML2,3
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 MDS3
OS exploratory subgroup analyses in patients ≥75 and <75 years1-3*
*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.1-3
HR based on the Cox proportional hazards model.2
ELN=European LeukemiaNet; HMA=hypomethylating agent; LVEF=left ventricular ejection fraction.
 
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.

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.
  • 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
 
Definitions of response assessments2
 
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 (glasdegib) + LDAC occurred within the first 6 months on treatment2
CR=complete response; CRi=complete response with incomplete blood count recovery; MLFS=morphologic leukemia-free state; MR=minor response; OS=overall survival; PR=partial response; PRi=partial response with incomplete blood count recovery; SD=stable disease.
 
In patients without unacceptable toxicity, treat for a minimum of 6 cycles to allow time for clinical response3
  • The median duration of treatment was 83 days (range, 3-972) with DAURISMO + LDAC and 47 days (range, 6-239 days) with LDAC alone3
 
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.