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FDA approves glasdegib for older patients with acute myeloid leukemia
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The FDA approved glasdegib for treatment of adults aged 75 years and older with newly diagnosed acute myeloid leukemia.
The approval of glasdegib (Daurismo, Pfizer) — a Hedgehog pathway inhibitor — applies to its use with low-dose cytarabine for patients who have comorbidities that preclude intensive induction chemotherapy.
“Intensive chemotherapy is usually used to control AML, but many adults with AML are unable to have intensive chemotherapy because of its toxicities. [This] approval gives health care providers another tool to use in the treatment of AML patients with various, unique needs,” 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, said in a press release.
The FDA based on the approval on results of the randomized, open-label BRIGHT AML 1003 trial, which included 115 patients with newly diagnosed AML who met at least one of the following criteria: age 75 years or older, severe cardiac disease, baseline ECOG performance status of 2, or baseline serum creatinine greater than 1.3 mg/dL.
Researchers randomly assigned 77 patients to glasdegib 100 mg daily plus low-dose cytarabine 20 mg subcutaneously twice daily on days 1 to 10 of each 28-day cycle. The other 38 patients received low-dose cytarabine alone. Treatment continued until disease progression or unacceptable toxicity.
OS served as the primary endpoint. Median follow-up was 20 months.
Patients assigned glasdegib achieved longer median survival (8.3 months vs. 4.3 months; HR = 0.46; 95% CI, 0.3-0.71).
“The [study] included patients with cardiac disease or mild to moderate kidney disease, who are often excluded from clinical trials,” Jorge Cortes, MD, deputy chair and professor of medicine in the department of leukemia at The University of Texas MD Anderson Cancer Center, said in a press release. “[Glasdegib] provides a much-needed treatment for those patients for whom intensive chemotherapy is not an option.”
The most common adverse reactions that occurred among at least 20% of glasdegib-treated patients in the first 90 days of therapy included anemia (43% for glasdegib plus cytarabine vs. 42% for cytarabine alone), fatigue (36% vs. 32%), hemorrhage (36% vs. 42%), febrile neutropenia (31% vs. 22%), musculoskeletal pain (30% vs. 17%), nausea (29% vs. 12%), edema (30% vs. 20%), thrombocytopenia (30% vs. 27%), dyspnea (23% vs. 24%), decreased appetite (21% vs. 7%), dysgeusia (21% vs. 2%), mucositis (21% vs. 12%), constipation (20% vs. 12%) and rash (20% vs. 7%).
The most common serious adverse reactions among glasdegib-treated patients included febrile neutropenia (29%), pneumonia (23%), hemorrhage (12%), anemia (7%) and sepsis (7%).
The glasdegib label includes a boxed warning for embryo-fetal toxicity.
The FDA previously granted glasdegib priority review and orphan drug designation.