On November 21, 2018, the FDA approved glasdegib (Daurismo; Pfizer), an oral Hedgehog inhibitor, in combination with low-dose cytarabine (LDAC), for patients with newly diagnosed acute myeloid leukemia (AML) who are aged ≥75 years or who have comorbidities that preclude use of intensive induction chemotherapy. The FDA approved glasdegib using its priority review and granted it an orphan drug designation.
This approval was based on a multicenter, open-label, randomized study of 115 patients with newly diagnosed AML who were aged ≥75 years, had severe cardiac disease, had a baseline Eastern Cooperative Oncology Group performance status 2, or had baseline serum creatinine >1.3 mg/dL. Patients were randomized in a 2:1 ratio to glasdegib 100 mg daily, with LDAC 20 mg subcutaneously twice daily on days 1 to 10 of a 28-day cycle or to LDAC alone in 28-day cycles until disease progression or unacceptable toxicity.
The primary end point was overall survival (OS). At a median follow-up of 20 months, the median OS was 8.3 months (95% confidence interval [CI], 4.4-12.2) with glasdegib plus LDAC versus 4.3 months (95% CI, 1.9-5.7) with LDAC alone (hazard ratio, 0.46; 95% CI, 0.30-0.71; P = .0002).
The most common (≥20%) side effects with glasdegib were anemia, fatigue, hemorrhage, febrile neutropenia, musculoskeletal pain, nausea, edema, thrombocytopenia, dyspnea, decreased appetite, dysgeusia, mucositis, constipation, and rash. Glasdegib has not been studied in patients with severe renal impairment or with moderate-to-severe hepatic impairment.