Recently, the FDA approved glasdegib (DaurismoÔ, Pfizer Labs) to be used in combination with low-dose cytarabine (LDAC) for newly diagnosed acute myeloid leukemia (AML) in elderly patients or those ineligible to receive intensive induction chemotherapy.
Richard Pazdur, MD, Director of the FDA's Oncology Center of Excellence and Acting Director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, explained, "Intensive chemotherapy is usually used to control AML, but many adults with AML are unable to have intensive chemotherapy because of its toxicities. Today's approval gives health care providers another tool to use in the treatment of AML patients with various, unique needs."
Approval of glasdegib was granted based on findings from a multicenter, open-label, randomized study (BRIGHT AML 1003, NCT01546038). In order to qualify for the study, participants had to meet at least one of the following criteria: be 75 years or older, have severe cardiac disease, have a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 2, or have a baseline serum creatinine >1.3 mg/dL. In 115 patients with newly diagnosed AML, glasdegib/LDAC improved median overall survival compared with LDAC alone (8.3 vs 4.3 months).
"The randomized phase 2 study, which formed the basis for today's approval, included patients with cardiac disease or mild to moderate kidney disease, who are often excluded from clinical trials. In the trial, [glasdegib] plus low-dose chemotherapy reduced the risk of death during the study period by 54% compared to chemotherapy alone. This provides a much-needed treatment for those patients for whom intensive chemotherapy is not an option," explained Jorge Cortes, MD, Deputy Chair and Professor of Medicine in the Department of Leukemia at the University of Texas MD Anderson Cancer Center.
Common side effects of glasdegib/LDAC include anemia, fatigue, hemorrhage, febrile neutropenia, musculoskeletal pain, nausea, edema, thrombocytopenia, dyspnea, decreased appetite, dysgeusia, mucositis, constipation, and rash.
Glasdegib/LDAC appears to be a promising new combination for patients with AML who require more stringent treatment guidelines.
For More Information
Clinicaltrials.gov (2018). A study to evaluate PF-04449913 with chemotherapy in patients with acute myeloid leukemia or myelodysplastic syndrome. NLM identifier: NCT01546038.