SYSTEMATIC LITERATURE REVIEW AND INDIRECT COMPARISON OF GLASDEGIB PLUS LOW DOSE ARA-C VERSUS A HYPOMETHYLATING AGENT FOR ACUTE MYELOID LEUKEMIA PATIENTS INELIGIBLE FOR INTENSIVE CHEMOTHERAPY
Author(s)
Forsythe A1, Arondekar B2, Tremblay G1, Chan G2, Su Y3
1Purple Squirrel Economics, New York, NY, USA, 2Pfizer Inc, Collegeville, PA, USA, 3Pfizer Inc, New York, NY, USA
OBJECTIVES: In a phase 2 randomized controlled study (RCT), glasdegib (GLAS) combined with Low Dose ARA-C (LDAC), showed significantly better overall survival (OS) vs LDAC alone in previously untreated acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy (NIC). Hypomethylating agents (HMAs), azacitidine (AZA) and decitabine (DEC) are considered current standard of care in this population. Our objective was to conduct an indirect treatment comparison (ITC) comparing OS for GLAS+LDAC vs. AZA and DEC. METHODS: Embase, MEDLINE, Cochrane database, and conference abstracts (ASCO, ESMO, ASH) were systematically searched through 12/2016 for relevant RCTs of GLAS, AZA and DEC in NIC AML patients. Classical frequentist ITC using the Bucher method compared OS hazards ratios (HRs), 95% confidence intervals (CI) using LDAC as the common comparator. RESULTS: Four studies met inclusion criteria: two comparing AZA to LDAC: Fenaux 2010; Dombret 2015; one comparing DEC to LDAC: Kantarjian 2012, and one comparing GLAS+LDAC to LDAC: Cortes 2016. Fenaux 2010 study was excluded due to population differences: baseline median bone marrow blasts at 23% in Fenaux 2010 vs. 49% in Cortes 2016. The remaining AZA and DEC studies were generally comparable in patient baseline characteristics to the GLAS study: age and cytogenic risk: age 75/73/76 years old, poor cytogenic risk 34%/37%/39%, in AZA/DEC/GLAS+LDAC, respectively. In the ITC, with LDAC as the common comparator, GLAS+LDAC compared favorably with indirect HR for OS vs. AZA and DEC being 0.51 (0.35-0.75) and 0.57 (0.40-0.80), respectively. CONCLUSIONS: Using ITC, treatment with GLAS+LDAC showed significantly better OS HR than AZA and DEC in previously untreated NIC AML patients. Limitations of current analysis include mixed IC & NIC population for the AZA trial, and mixed comparator arm of both LDAC and BSC for the DEC trial. Analyses using patient-level data matching baseline characteristics across studies may enable more robust ITC.
Conference/Value in Health Info
2017-11, ISPOR Europe 2017, Glasgow, Scotland
Value in Health, Vol. 20, No. 9 (October 2017)
Code
PCN21
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Oncology, Systemic Disorders/Conditions