@article{e168dab3419348b28fca00bc4bcb7021,
title = "Glasdegib in combination with cytarabine and daunorubicin in patients with AML or high-risk MDS: Phase 2 study results",
abstract = "Glasdegib is a Hedgehog pathway inhibitor. This ongoing, open-label, phase 2 study (NCT01546038) evaluated glasdegib plus cytarabine/daunorubicin in patients with untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS). Patients received glasdegib 100 mg orally, once daily in continuous 28-day cycles from day −3, with intravenous cytarabine 100 mg/m2 on days 1-7 and daunorubicin 60 mg/m2 on days 1-3. Patients in remission then received consolidation therapy (2-4 cycles of cytarabine 1 g/m2 twice daily on days 1, 3, 5 of each cycle), followed by maintenance glasdegib (maximum 6 cycles). Primary endpoint was complete remission (CR) in patients aged ≥55 years. Secondary endpoints included overall survival (OS), safety and outcome by mutational status. Patients had a median (range) age of 64.0 (27-75) years, 60.0% were male, and 84.5% were white. In 69 evaluable patients, 46.4% (80% confidence interval [CI]: 38.7-54.1) achieved investigator-reported CR. Among patients ≥55 years old (n = 60), 40.0% (80% CI 31.9-48.1) achieved CR. Among all 69 patients, median OS was 14.9 (80% CI 13.4-19.3) months, with 12-month survival probability 66.6% (80% CI 58.5-73.4). The most common treatment-related adverse events (≥50% patients) were diarrhea and nausea. There were no significant associations between mutational status (12 genes) and clinical response, suggesting potential benefit across diverse molecular profiles. Glasdegib plus cytarabine/daunorubicin was well tolerated and associated with clinical activity in patients with untreated AML or high-risk MDS. A randomized phase 3 trial of glasdegib in combination with chemotherapy (7 + 3 schedule) is ongoing.",
author = "Cortes, {Jorge E.} and {Douglas Smith}, B. and Wang, {Eunice S.} and Akil Merchant and Oehler, {Vivian G.} and Martha Arellano and DeAngelo, {Daniel J.} and Pollyea, {Daniel A.} and Sekeres, {Mikkael A.} and Tadeusz Robak and Ma, {Weidong Wendy} and Mirjana Zeremski and {Naveed Shaik}, M. and {Douglas Laird}, A. and Ashleigh O'Connell and Geoffrey Chan and Schroeder, {Mark A.}",
note = "Funding Information: Jorge E. Cortes: I have research support and have worked as a paid consultant for Pfizer, Jazz Pharmaceuticals, Novartis, Astellas, Daiichi and Immunogen. B. Douglas Smith: Advisory Board and Consultant for Celgene, Jazz Pharmaceuticals, Novartis, Pfizer. Eunice S. Wang: I have served on advisory board and as a speaker for Pfizer. Akil Merchant: is an advisory board member for Agios, Pfizer and Takeda and has received research funding from Pfizer. Vivian G. Oehler: has served as an advisory board member for Pfizer. Martha Arellano: Received funding for research from Cephalon oncology. Daniel J. DeAngelo: is an advisory board member for Amgen, Pfizer, Celgene, Takeda, Shire, Jazz, Incyte and Novartis, and has received research funding from Abbvie. Daniel A. Pollyea: has served as an advisory board member for Pfizer, Servier, Takeda, Cusi, Celgene, Agios, AbbVie and Celyad, and has received research funding from Pfizer and Agios. Mikkael A. Sekeres: is an advisory board member for Celgene. Tadeusz Robak: research grant from Pfizer. Mark A. Schroeder has no conflicts of interest to disclose for this study. Weidong Wendy Ma, Mirjana Zeremski, M. Naveed Shaik, A. Douglas Laird, Ashleigh O'Connell and Geoffrey Chan are employees and shareholders of Pfizer Inc. Funding Information: The authors thank the patients and their families/caregivers, and the investigators, research nurses, study coordinators, and operations staff who contributed to this study. DNA sequencing data were generated by Mark Ozeck, Stephen Huang, Keith Ching and colleagues, at Pfizer, La Jolla, CA, USA. This study was sponsored by Pfizer Inc. Medical writing and editorial support were provided by Anne Marie McGonigal, PhD, of Engage Scientific Solutions and funded by Pfizer Inc.",
year = "2018",
month = nov,
doi = "10.1002/ajh.25238",
language = "English (US)",
volume = "93",
pages = "1301--1310",
journal = "American Journal of Hematology",
issn = "0361-8609",
publisher = "Wiley-Liss Inc.",
number = "11",
}