Combination glasdegib and low-dose cytarabine improves AML patients’ survival more than azacitidine or decitabine, study suggests

Written by Ilana Landau, Editor

In a novel study, researchers employed indirect and simulated treatment comparison methods to assess the comparative effectiveness of combination glasdegib and low-dose cytarabine for older patients with acute myeloid leukemia (AML), over azacitidine or decitabine.

In 2018, the US FDA approved the use of combination glasdegib and low-dose cytarabine for older patients with acute myeloid leukemia (AML) — a disease, and patient cohort, for which few other therapies are viable. Now, for the first time, an international team of researchers from Purple Squirrel Economics, Pfizer (both NY, USA) and the Institute of Health & Wellbeing (Glasgow, UK) have employed novel study methodologies to determine whether this pharmacotherapy combination offers improved overall survival for patients, compared with traditionally administered drugs including azacitidine or decitabine.

Due to unfavorable prognostic factors associated with patients’ ages and other comorbidities, treatment options for older patients with AML are highly restricted and their 5-year, post-diagnosis survival rates are significantly lower than those of younger AML patients. 

In 2018, following the publication of results from a Phase II clinical trial evaluating the comparative effectiveness of combination glasdegib and low-dose cytarabine against glasdegib alone, the FDA approved the combination for older patients with AML.

To assess the relative efficacy of combination glasdegib and low-dose cytarabine compared with traditionally administered azacitidine or decitabine monotherapies, researchers employed an indirect treatment comparison methodology.

Frequently asked questions:

To ensure between-trial differences were adjusted for, simulated treatment comparison methods were utilized.

According to the results from both indirect and simulated treatment comparison studies, patients’ overall survival on combination glasdegib and low-dose cytarabine was significantly greater compared with patients who received either azacitidine or decitabine monotherapies.

In the study, the authors stated: “The stepwise, exponential and Weibull simulated treatment comparison models adjusting for key covariates resulted in the optimal model fit and the lowest hazard ratios, which demonstrated glasdegib and low-dose cytarabine superiority to azacitidine and to decitabine.”

The authors concluded: “Regardless of the modelling technique used, both indirect treatment comparison and simulated treatment comparison consistently demonstrated significantly improved overall survival for glasdegib and low-dose cytarabine relative to azacitidine or decitabine.”


Tremblay G, Westley T, Cappelleri JC et al. Overall survival of glasdegib in combination with low-dose cytarabine, azacitidine, and decitabine among adult patients with previously untreated AML: comparative effectiveness using simulated treatment comparisons. Clin. Outcomes Res. (Epub ahead of print) (2019).

What is AML?

AML is a form of cancer characterized by the bone marrow’s abnormal production of red blood cells, platelets or certain white blood cells. 

What is the mechanism of action of glasdegib?

Glasdegib (Daurismoâ„¢) is an orally administered inhibitor of the Hedgehog signaling pathway. Hyperactivity of hedgehog signaling can be associated with tumor cell growth. 

How do azacitidine and decitabine work?

Azicitidine (Vidaza®)and decitabine (Dacogen) are both hypomethylating agents. They act to inhibit the enzyme DNA methyltransferase. This effectively limits the division, replication and growth of cancer cells.